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Emerging roles of circular RNAs in retinal diseases

Neural Regeneration Research 2022年第9期17卷 1875-1880页

作者： Aneliya Hanineva Karen Sophia Park Joshua J.Wang Margaret M.DeAngelis Michael H.Farkas Sarah X.Zhang Department of Ophthalmology and Ross Eye Institute Jacobs School of Medicine and Biomedical SciencesUniversity at BuffaloState University of New YorkBuffaloNYUSA Research Service Veterans Administration Western New York Healthcare SystemBuffaloNYUSA Department of Biochemistry Jacobs School of Medicine and Biomedical SciencesUniversity at BuffaloState University of New YorkBuffaloNYUSA

Retinal disorders are a group of ocular diseases whose onset is associated with a number of aberrant molecular and cellular processes or physical damages that affect retinal structure and function resulting in neural and vascular degeneration in the *** research has primarily focused on delaying retinal disease with minimal success in preventing or reversing neuronal *** this review,we explore a relatively new field of research involving circular RNAs,whose potential roles as biomarkers and mediators of retinal disease pathogenesis have only just *** knowledge of circular RNAs function is limited given its novelty,current evidence has highlighted their roles as modulators of microRNAs,regulators of gene transcription,and biomarkers of disease development and ***,we summarize how circular RNAs may be implicated in the pathogenesis of common retinal diseases including diabetic retinopathy,glaucoma,proliferative vitreoretinopathy,and age-related macular ***,we explore the potential of circular RNAs as novel biomarkers and therapeutic targets for the diagnosis and treatment of retinal diseases.

关键词： age-related macular degeneration circular RNA diabetic retinopathy glaucoma microRNA proliferative vitreoretinopathy retina

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Diminished fracture initiation sites in ceramic layers bonded to glow-discharge treated substructure

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Open Journal of Stomatology 2013年第6期3卷 307-313页

作者： Hyeongil Kim Edward A. Monaco Jr. Frederick McIntyre Elaine L. Davis Robert E. Baier Department of Oral Diagnostic Sciences University at Buffalo New York USA Department of Restorative Dentistry University at Buffalo New York USA va western new york healthcare system at buffalo New York USA

A mechanically retentive structure and meticulous surface cleanliness are critical factors in providing fracture resistance and clinical success of metal ceramic restorations. This investigation compared the porcelain/metal interfaces of deliberate compressive fractures of ceramic crowns between conventional preparation and application of the Radio Frequency Glow Discharge Treatment (RFGDT) before each bonding step. It evaluated RFGDT’s capacity to improve wetting effectiveness and minimize porosity. Twelve metal ceramic crowns were fabricated identically. RFGDT was applied to the metal substructures of half the specimens before the ceramic layering process. All specimens were fractured in the same manner by an applied compressive force to simulate dental occlusive failure. Fracture surfaces were inspected by light and scanning electron microscopy. Quantitative analyses of images were performed to identify numbers, locations of cracks, porosity patterns, and other morphological correlates of the fracture zones. There were significantly fewer voids per millimeter at the interfaces in the RFGDT group than in the non-RFGDT group (t = 2.377, df = 9, p = 0.021). There was a significant difference in the number of horizontal cracks per millimeter between the groups (t = 2.132, df = 7, p = 0.035), with more cracks occurring in the non-RFGDT group. RFGDT can improve the integrity of metal ceramic crowns by increasing the substratum surface energy, improving porcelain wetting and spreading and thereby diminishing the numbers of interfacial voids available for initiation of fracture. Routine application of RFGDT should result in fewer cracks along metal/ceramic interfaces in all restorative preparations.

关键词： Porcelain Fracture Glow Discharge Treatment Metal Ceramic Crown Porosity Surface Energy

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Superior safety of direct oral anticoagulants compared to Warfarin in patients with atrial fibrillation and underlying cancer: a national veterans affairs database study

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Journal of Geriatric Cardiology 2019年第9期16卷 706-709页

作者： Abhishek C Sawant Arnav Kumar Wilmon Mccray Sheldon Tetewsky Linda Parone Srilekha Sridhara Meghana Prakash Hiriyur Prakash Gary Tse Tong LIU Nidhi Kanwar Aishwarya Bhardwaj Sahoor Khan Christopher Manion Ankush Lahoti Ashish Pershad Peter Elkin John Corbelli Banner University Medical Center Phoenix Arizona USA Andreas Gruentzig Cardiovascular Center Emory University School of Medicine Cardiovascular Medicine Atlanta GA USA western new york healthcare system Buffalo VA Medical Center Buffalo NY USA Department of Medicine and Therapeutics Faculty of Medicine Chinese University of Hong Kong Hong Kong SAR China Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular disease Department of Cardiology Tianjin Institute of Cardiology Second Hospital of Tianjin Medical University Tianjin China

Background Studies evaluating safety of warfarin and direct oral anticoagulants(DOACs) for prevention of stroke in patients with atrial fibrillation(AF) are lacking. Methods & Results All patients(n = 196,521) receiving care at veteran’s affairs with active cancer and AF from 2010–2015 were included. One-year mortality was significantly higher in unadjusted analysis with warfarin(44.9%) compared to dabigatran(25%, P varoxaban(24.4%, P varoxaban(0.7%) and apixaban(0.8%) respectively, P = 0.04. Conclusions We demonstrated the superior safety profile of DOACs compared to warfarin among patients with underlying cancer and AF. Warfarin was associated with higher mortality, similar ischemic stroke risk but higher risk of hemorrhagic stroke.

关键词： Atrial fibrillation Cancer Oral anticoagulation

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Understanding that Addiction Is a Brain Disorder Offers Help and Hope

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Health 2022年第6期14卷 684-695页

作者： Kenneth Blum Abdalla Bowirrat David Baron Rajendra D. Badgaiyan Panayotis K. Thanos Igor Elman Eric R. Braverman Mark S. Gold Division of Addiction Research & Education Center for Psychiatry Medicine & Primary Care (Office of the Provost) Western University Health Sciences Pomona USA Department of Molecular Biology and Adelson School of Medicine Ariel University Ariel Israel Department of Psychiatry South Texas Veteran Health Care System Audie L. Murphy Memorial VA Hospital and Long School of Medicine University of Texas Health Science Center San Antonio USA Department of Psychiatry MT. Sinai School of Medicine New York USA Department of Psychology & Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions (BNNLA) Research Institute on Addictions University at Buffalo Buffalo USA Department of Psychiatry Harvard School of Medicine Cambridge USA Division of Personalized Medicine The Kenneth Blum Behavioral & Neurogenetic Institute (Division of iVitalize Inc.) Austin USA Department of Psychiatry Washington University School of Medicine St. Louis USA

We refute the controversial statement that addiction is not a brain disorder. Extensive peer-reviewed studies support the underlying neurobiological and neurogenetic basis of addiction’s “disease model”. In the 70s and 80s, a few clinical scientists suggested that it is possible to use behavioral training to teach controlled drinking. However, this controversial model failed drastically and increased labeling and stigmatization. Additionally, it was unhelpful in the search for treatment. Instead, we assert that addiction is a neuropsychiatric disorder characterized by a recurring desire to continue taking substances despite harmful physical and mental consequences. Work from our laboratory in 1995 supported the Reward Deficiency Syndrome (RDS) concept based on a common neurogenetic mechanism (hypodopaminergia) that underlies all substance and non-substance addictions. Non-substance addictions include behaviors like pathological gambling, internet addiction, and mobile phone addiction. Certain impulsive and compulsive behaviors or the acute intake of psychoactive substances result in heightened dopaminergic activity, while the opposite, hypodopaminergia, occurs following chronic abuse. Patients with Substance Use Disorder (SUD) can have a genetic predisposition compounded by stress or other epigenetic insults that can impact recovery. Relapse will occur post-short-term recovery if dopaminergic dysfunction remains untreated. Addiction, a brain disorder, requires treatment with DNA-directed pro-dopamine regulation and rehabilitation.

关键词： Reward Deficiency Syndrome Abstinence Controlled Drinking Neurogenetic Brain Disorder

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Hypothesizing That Pediatric Autoimmune Neuropsychiatric Associated Streptococcal (PANDAS) Causes Rapid Onset of Reward Deficiency Syndrome (RDS) Behaviors and May Require Induction of “Dopamine Homeostasis”

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Open Journal of Immunology 2022年第3期12卷 65-75页

作者： Kenneth Blum Catherine A. Dennen Eric R. Braverman Ashim Gupta David Baron Bernard William Downs Debasis Bagchi Panayotis Thanos Maureen Pollock Jag Khalsa Igor Elman Abdalla Bowirrat Rajendra D. Badgaiyan Center for Mental Health and Sports Psychiatry Western University Health Sciences Pomona USA The Kenneth Blum Behavioral & Neurogenetic Institute Austin USA Department Psychiatry Boonshoff School of Medicine Wright University Dayton USA Institute of Psychology ELTE E&#246tv&#246s Loránd University Budapest Hungary Department of Psychiatry School of Medicine University of Vermont Burlington USA Division of Nutrigenomics Victory Nutrition International Inc. Bonita Springs USA Department of Molecular Biology Adelson School of Medicine Ariel University Ariel Israel Department of Family Medicine Jefferson Health Northeast Philadelphia USA Future Biologics Lawrenceville USA Department of Pharmaceutical Sciences Texas Southern University Houston USA Department of Psychology & Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions (BNNLA) Research Institute on Addictions University at Buffalo Buffalo USA Department of Microbiology Immunology and Tropical Medicine School of Medicine George Washington University Washington DC USA Cambridge Health Alliance Harvard Medical School Cambridge USA Department of Psychiatry Ichan School of Medicine at Mount Sinai New York USA Department of Psychiatry South Texas Veteran Health Care System Audie L. Murphy Memorial VA Hospital Long School of Medicine University of Texas Health Science Center San Antonio USA

Pediatric autoimmune neuropsychiatric disorders associated with group A streptococcal infections (PANDAS) is a concept that is used to characterize a subset of children with neuropsychiatric symptoms, tic disorders, or obsessive-compulsive disorder (OCD), whose symptoms are exacerbated by group A streptococcal (GAS) infection. PANDAS has been known to cause a sudden onset of reward deficiency syndrome (RDS). RDS includes multiple disorders that are characterized by dopaminergic signaling dysfunction in the brain reward cascade (BRC), which may result in addiction, depression, avoidant behaviors, anxiety, tic disorders, and/or OCD. According to research by Blum et al., the dopamine receptor D2 (DRD2) gene polymorphisms are important prevalent genetic determinants of RDS. The literature demonstrates that infections like Borrelia and Lyme, as well as other infections like group A beta-hemolytic streptococcal (GABHS), can cause an autoimmune reaction and associated antibodies target dopaminergic loci in the mesolimbic region of the brain, which interferes with brain function and potentially causes RDS-like symptoms/behaviors. The treatment of PANDAS remains controversial, especially since there have been limited efficacy studies to date. We propose an innovative potential treatment for PANDAS based on previous clinical trials using a pro-dopamine regulator known as KB220 variants. Our ongoing research suggests that achieving “dopamine homeostasis” by precision-guided DNA testing and pro-dopamine modulation could result in improved therapeutic outcomes.

关键词： PANDAS CANS Reward Deficiency Syndrome Group A Beta-Hemolytic Streptococcal (GABHS) Pro-Dopamine Regulation Dopamine Homeostasis Molecular Mimicry Lyme Borrelia

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