Medical Specialties Commons^™

Antisense Oligonucleotide Therapy Rescues Disturbed Brain Rhythms And Sleep In Juvenile And Adult Mouse Models Of Angelman Syndrome, Dongwon Lee, Wu Chen, Heet Naresh Kaku, Xinming Zhuo, Eugene S Chao, Armand Soriano, Allen Kuncheria, Stephanie Flores, Joo Hyun Kim, Armando Rivera, Frank Rigo, Paymaan Jafar-Nejad, Arthur L Beaudet, Matthew S Caudill, Mingshan Xue

Faculty, Staff and Students Publications

UBE3A encodes ubiquitin protein ligase E3A, and in neurons its expression from the paternal allele is repressed by the UBE3A antisense transcript (UBE3A-ATS). This leaves neurons susceptible to loss-of-function of maternal UBE3A. Indeed, Angelman syndrome, a severe neurodevelopmental disorder, is caused by maternal UBE3A deficiency. A promising therapeutic approach to treating Angelman syndrome is to reactivate the intact paternal UBE3A by suppressing UBE3A-ATS. Prior studies show that many neurological phenotypes of maternal Ube3a knockout mice can only be rescued by reinstating Ube3a expression in early development, indicating a restricted therapeutic window for Angelman syndrome. Here, we …

Mitochondrial Dysfunction Reactivates Α-Fetoprotein Expression That Drives Copper-Dependent Immunosuppression In Mitochondrial Disease Models, Kimberly A Jett, Zakery N Baker, Amzad Hossain, Aren Boulet, Paul A Cobine, Sagnika Ghosh, Philip Ng, Orhan Yilmaz, Kris Barreto, John Decoteau, Karen Mochoruk, George N Ioannou, Christopher Savard, Sai Yuan, Osama Hmh Abdalla, Christopher Lowden, Byung-Eun Kim, Hai-Ying Mary Cheng, Brendan J Battersby, Vishal M Gohil, Scot C Leary

Faculty, Staff and Students Publications

Signaling circuits crucial to systemic physiology are widespread, yet uncovering their molecular underpinnings remains a barrier to understanding the etiology of many metabolic disorders. Here, we identified a copper-linked signaling circuit activated by disruption of mitochondrial function in the murine liver or heart that resulted in atrophy of the spleen and thymus and caused a peripheral white blood cell deficiency. We demonstrated that the leukopenia was caused by α-fetoprotein, which required copper and the cell surface receptor CCR5 to promote white blood cell death. We further showed that α-fetoprotein expression was upregulated in several cell types upon inhibition of oxidative …

Epidemiological/Disease And Economic Burdens Of Cervical Cancer In 2010–2014: Are Younger Women At Risk?, Chuhao Xi, Jay J. Shen, Betty Burston, Soumya Upadhyay, Shoujun Zhou

Healthcare Administration and Policy Faculty Research

Objective: Cervical cancer is an important factor threatening women’s health in China. This study examined the epidemiological and economic burden of cervical cancer among the medically insured population, which could provide data support for government departments to formulate policies. Methods: All new cases of cervical cancer under the Urban Employee Basic Medical Insurance (UEBMI) plan in a provincial capital city in eastern China from 2010 to 2014 were collected. The Cox proportional hazard model was used to analyze the factors affecting the survival rates for cervical cancer. Outpatient and hospitalization expenses were used to assess the direct economic burden, and …

Medical Training Of Seafarers: International Maritime Health Foundation (Imhf) Expert Panel Consensus Statement, Nebojša Nikolić, Jon Magnus Haga, Jens Tülsner, Per Otto Årland, Alf Magne Horneland, Bill Kavanagh, Klaus Seidenstucker, Spike Briggs, Inger Lund-Kordahl, Cecilia Simolin Pernilla

Articles

Background: Medical emergencies and on-going medical conditions on board may seriously impair seafarers’ health and safety, and also negatively impact on future work prospects for seafarers. When a seafarer gets ill or injured on a ship, medical treatment often relies on the competences on his colleagues on board. The aim of this project was to establish a consensus-based minimum standard for medical education for seafarers, in order to ensure competency for adequate management of ill-health on board.

Materials and methods: International Maritime Health Foundation (IMHF) conducted a workshop on medical training of seafarers. A research-based approach to gain consensus on …

Fn14-Directed Dart Nanoparticles Selectively Target Neoplastic Cells In Preclinical Models Of Triple-Negative Breast Cancer Brain Metastasis, Christine P Carney, Anshika Kapur, Pavlos Anastasiadis, Rodney M Ritzel, Chixiang Chen, Graeme F Woodworth, Jeffrey A Winkles, Anthony J Kim

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) patients with brain metastasis (BM) face dismal prognosis due to the limited therapeutic efficacy of the currently available treatment options. We previously demonstrated that paclitaxel-loaded PLGA−PEG nanoparticles (NPs) directed to the Fn14 receptor, termed “DARTs”, are more efficacious than Abraxane—an FDA-approved paclitaxel nanoformulation—following intravenous delivery in a mouse model of TNBC BM. However, the precise basis for this difference was not investigated. Here, we further examine the utility of the DART drug delivery platform in complementary xenograft and syngeneic TNBC BM models. First, we demonstrated that, in comparison to nontargeted NPs, DART NPs exhibit preferential association …

Inherited Human Itk Deficiency Impairs Ifn-Γ Immunity And Underlies Tuberculosis, Masato Ogishi, Rui Yang, Rémy Rodriguez, Dominic P Golec, Emmanuel Martin, Quentin Philippot, Jonathan Bohlen, Simon J Pelham, Andrés Augusto Arias, Taushif Khan, Manar Ata, Fatima Al Ali, Flore Rozenberg, Xiao-Fei Kong, Maya Chrabieh, Candice Laine, Wei-Te Lei, Ji Eun Han, Yoann Seeleuthner, Zenia Kaul, Emmanuelle Jouanguy, Vivien Béziat, Leila Youssefian, Hassan Vahidnezhad, V Koneti Rao, Bénédicte Neven, Claire Fieschi, Davood Mansouri, Mohammad Shahrooei, Sevgi Pekcan, Gulsum Alkan, Melike Emiroğlu, Hüseyin Tokgöz, Jouni Uitto, Fabian Hauck, Jacinta Bustamante, Laurent Abel, Sevgi Keles, Nima Parvaneh, Nico Marr, Pamela L Schwartzberg, Sylvain Latour, Jean-Laurent Casanova, Stéphanie Boisson-Dupuis

Department of Dermatology and Cutaneous Biology Faculty Papers

Inborn errors of IFN-γ immunity can underlie tuberculosis (TB). We report three patients from two kindreds without EBV viremia or disease but with severe TB and inherited complete ITK deficiency, a condition associated with severe EBV disease that renders immunological studies challenging. They have CD4+ αβ T lymphocytopenia with a concomitant expansion of CD4-CD8- double-negative (DN) αβ and Vδ2- γδ T lymphocytes, both displaying a unique CD38+CD45RA+T-bet+EOMES- phenotype. Itk-deficient mice recapitulated an expansion of the γδ T and DN αβ T lymphocyte populations in the thymus and spleen, respectively. Moreover, the patients' T lymphocytes secrete small amounts of IFN-γ in …

Repurposing Ms Immunotherapies For Cidp And Other Autoimmune Neuropathies: Unfulfilled Promise Or Efficient Strategy?, Felix Kohle, Marinos Dalakas, Helmar C Lehmann

Department of Neurology Faculty Papers

Despite advances in the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and other common autoimmune neuropathies (AN), still-many patients with these diseases do not respond satisfactorily to the available treatments. Repurposing of disease-modifying therapies (DMTs) from other autoimmune conditions, particularly multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), is a promising strategy that may accelerate the establishment of novel treatment choices for AN. This approach appears attractive due to homologies in the pathogenesis of these diseases and the extensive post-marketing experience that has been gathered from treating MS and NMOSD patients. The idea is also strengthened by a number …

Infiltrating Cd8+ T Cells Exacerbate Alzheimer’S Disease Pathology In A 3d Human Neuroimmune Axis Model, Jefin Jose, Devam Purohit

VCU's Medical Journal Club: The Work of Future Health Professionals

In this study, Jorfi et al. employed a neuroimmune axis model containing neurons, astrocytes, and microglia to examine the role of immune cells in Alzheimer's disease. Jorfi et al. found that T cells selectively infiltrated the BRAIN compartment of the neuroimmune axis model as compared to B cells and monocytes. Jorfi et al. further found that CD8+ T cells demonstrated heightened cytotoxicity in the Alzheimer's disease brain, illuminating the role of immune cells in neurodegeneration. Upon further examination, the CXCR3-CXCL10 signaling pathway was found to have an important role in inflammation.

A Genome-Wide In Vivo Crispr Screen Identifies Essential Regulators Of T Cell Migration To The Cns In A Multiple Sclerosis Model, Jefin Jose

VCU's Medical Journal Club: The Work of Future Health Professionals

Kendirli et al. (2023) used a CRISPR screen to determine the proteins involved in T cell migration into the CNS in multiple sclerosis. Overall, eighteen facilitators and five brakes to T cell infiltration into the CNS were identified. Kendirli et al. specifically identified ITGA4, FERMT3, and HSP90B1 to make up the adhesion module, CXCR3, GNAI2, and TBX21 to make up the chemotaxis module, and GRK2 and S1PR2 to make up the egress module. This study demonstrated the ability of a CRISPR screen to identify elements in a disease process and thus identify targets for future multiple sclerosis therapies.

Effects Of Meditation On Chronic Pain Management Among Older Adults, Katelyn R. Forsell

Doctor of Nursing Practice

The older adult population is expected to continue to grow. This population is more susceptible to facing chronic health conditions that often contribute to pain. Pain affects many aspects of an individual's life and can be debilitating, affecting physical and mental wellbeing. Chronic pain among older adults is often not well managed. Mindfulness meditation is a holistic healing modality that literature supports for pain mitigation (Creswell & Khoury, 2019). This scholarly project provided mindfulness meditation sessions to older adults in an independent and assisted living facility setting to help educate and guide them in reducing chronic pain. Pain reduction scores …

Play's Continuum Of Needs: Building Blocks For Deepening Play Opportunities In Medical Environments, Deborah Brewster Vilas

Graduate School of Education

Optimal healing for children in hospitals occurs when their developmental needs are considered as part of their overall treatment plan. One of the most pressing developmental needs for all children is the need to play, and this remains so even when they are confined to a hospital bed or face developmental delays or disabilities. This chapter examines the most basic components of implementing play programs in hospitals, such as the intentional creation of space for play, determining the best times for children to play, and exploring what types of play are therapeutic and possible in a hospital environment. The author …

Pupillometry, Elizabeth Plante, Casey Schmidt

Nursing Posters

Background:

• Measuring pupillary light reflex is a standard part of neurological assessment.
• Changes in pupil reactivity may indicate unfavorable outcomes, such as increased intracranial pressure and brain herniation.
• Physiologic and pharmacologic agents may affect pupil reactivity.
• In some instances, pupillary light reflex is the only piece of neurologic assessment readily testable.

Importance Of Eye Exams As A Secondary Preventative Measure For Diabetic Retinopathy: Winning The War On Blindness, Alondra S. Arredondo, Olivia Demeyer, Rachel Louise Pfenning-Wendt, Samuel Wolfe

All Electronic Theses and Dissertations

Despite current efforts by medical professionals to reduce the prevalence of diabetic retinopathy (DR), a microvascular complication of uncontrolled diabetes, this noncommunicable disease remains the leading cause of preventable vision loss worldwide (Cheloni et al., 2019). Research estimates 90% of DR cases could be prevented if detected early through routine eye exams, yet certain social determinants of health still remain a significant barrier for many individuals to receive this care. According to Wong & Sabanayagam (2020), only 25% of DM patients in developing countries receive routine care with adequate eye screenings. The goal of this community service project was to …

Leukocytes As Mediators Of Gut-Brain Communication, Dilini Ekanayake

Biomedical Sciences Posters and Presentations

Food allergies

▪ Reactions range from mild/delayed to severe/rapid. ▪ People with mild allergic reactions have increased re-exposure risks. ▪ Cow’s milk allergy tends to manifest with milder allergic reactions.

Cow’s milk allergy (CMA)

▪ CMA has been associated with behavioral and neurological disorders. ▪ How allergic inflammatory signals from the gut reach the brain is unclear

Continuous Consumption Of Whey Protein Affects Motor And Cognitive Functions In A Mouse Model Of Cow’S Milk Hypersensitivity, Geetika Verma

Biomedical Sciences Posters and Presentations

Hypersensitization to a food allergen can occur in the absence of immediate allergic reactions, a condition referred to as asymptomatic sensitization. Using mice asymptomatically sensitized to a bovine whey allergen, β-lactoglobulin (BLG, Bos d 5), we have previously shown that chronic exposure to the allergen results in behavior changes with increased neuroinflammation and cortical demyelination. However, whether allergen avoidance can resolve these pathologies is unknown. Thus, we aimed to compare immunological and behavioral changes in sham- or BLG-sensitized mice with or without the removal of dietary whey after the mice had consumed either a control diet (CTL) or a whey-protein-containing …

Continued Food-Allergen Consumption Exacerbates Beta-Amyloid Accumulation In Allergen-Sensitized Appnl-G-Fmice., Afrina Brishti

Biomedical Sciences Posters and Presentations

Alzheimer’s disease (AD) is the most common neurodegenerative disease, with β-amyloid(Aβ) plaque deposition being one of the hallmark pathologies. However, the etiology of AD remains elusive. While chronic inflammation from recurrent infections or injury seems to contribute to AD development, it is unclear whether atopic diseases, such as allergies, are associated with AD. We previously reported that continuous consumption of a whey protein(WP) -containing diet led to lasting neuro inflammation in C57BL/6J mice that were sensitized but tolerant to a bovine milk allergen, β-lactoglobulin (BLG;Bosd5). Thus, we hypothesized that the persisting neuroinflammation due to repeated allergen consumption would exacerbate AD …

New England Osteopathic Association: Constitution, New England Osteopathic Association

John McPartland, D.O. Collection

Constitution of the New England Osteopathic Association organized in Boston January 28, 1905.

Vermont State Association Of Osteopathic Physician And Surgeons Inc.: Correspondence Soliciting New D.O.S To Vermont, Vermont State Association Of Osteopathic Physicians And Surgeons Inc.

John McPartland, D.O. Collection

A letter from the Vermont State Association of Osteopathic Physicians and Surgeons, Inc. soliciting D.O.s to move to Vermont.

Nefom: Board Of Trustees: Corporation Members, New England Foundation For Osteopathic Medicine

William Kirmes, D.O. Collection

List of NEFOM corporation members, undated.

New England Osteopathic Assembly: Maxwell To Kirmes, R. E. Maxwell D.O.

William Kirmes, D.O. Collection

A short handwritten personal note from Dr. R.E. Maxwell to Dr. Kirmes arranging their trip to the New England Osteopathic Assembly meeting.

New Hampshire Osteopathic Association: Dr. Kirmes To Potential New Hampshire D.O.S, William Kirmes D.O.

William Kirmes, D.O. Collection

A letter from Dr. Kirmes to potential New Hampshire D.O.s recommending coming to New Hampshire to practice.

Rapid Onset Hydralazine-Induced Antineutrophil Cytoplasmic Antibody (Anca) Associated Vasculitis Presenting With Hemoptysis And Kidney Failure: Case Report, Rachel E. Easter, Andinet Gizaw, Natalie Klein

Internal Medicine Publications

Hydralazine-induced vasculitis can be challenging to recognize and diagnose as presenting symptoms vary and can mimic other conditions or diseases, however, swift intervention and treatment is key in halting progression of the disease and providing patients with the best possible outcomes. A 71-year-old African American female presented to the emergency department with weakness, fatigue, anemia, blood-streaked sputum, fever, chills, and severe myalgias. Hydralazine was prescribed to treat resistant hypertension eight months prior to presentation. Hydralazine was discontinued on hospital day (HD) 4. Pertinent laboratory values showed elevated inflammatory markers, positive antinuclear antibody (ANA), negative rheumatoid factor (RF), normal complement levels, …

Chesterfield Fire And Ems Mobile Integrated Healthcare: Background And A Case Study, David Bigelow

Case Studies from Age in Action

Learning Objectives

• Explain the history of Mobile Integrated Healthcare.
• Understand the importance of reducing hospital readmissions.
• Learn how MIH partners with Adult Protective Services and others for the benefit of their patients.

Adult Day Services: A Model That Works, Heather Turbyne-Pollard

Case Studies from Age in Action

Learning Objectives

1. Demonstrate the need for adult day services.

2. Illustrate the benefits beyond those to the older adults served.

3. Demystify common misconceptions about adult day services.

Care At The Intersections: A Case Study, Alyssa Camp

Case Studies from Age in Action

Learning Objectives

1. Increase understanding of trans elder care.

2. Recognize the ethical considerations of caring for a trans elder with dementia.

3. Understand the value of LGBTQ+ training and programing in assisted living.

Improving Comfort And Confidence With Advance Care Planning In Primary Care, Thomas Krajewski, Donald Courtney, Tyler Kilgore

South Atlantic Division GME Research Day 2023

No abstract provided.

Citrullinated And Malondialdehyde-Acetaldehyde Modified Fibrinogen Activates Macrophages And Promotes An Aggressive Synovial Fibroblast Phenotype In Patients With Rheumatoid Arthritis, Nozima Aripova, Michael J. Duryee, Bryant England, Carlos D. Hunter, Jack E. Mordeson, Evan Ryan, Eric C. Daubach, Debra J. Romberger, Geoffrey M. Thiele, Ted R. Mikuls

Journal Articles: Internal Medicine

Objective: Post-translational protein modifications with malondialdehyde-acetaldehyde (MAA) and citrulline (CIT) are implicated in the pathogenesis of rheumatoidarthritis (RA). Although precise mechanisms have not been elucidated, macrophage-fibroblast interactions have been proposed to play a central role in the development and progression of RA. The purpose of our study was to evaluate the downstream effects of macrophage released soluble mediators, following stimulation with fibrinogen (FIB) modified antigens, on human fibroblast-like synoviocytes (HFLS).

Methods: PMA-treated U-937 monocytes (Mϕ) and macrophage-differentiated peripheral blood mononuclear cells (MP) were stimulated with FIB, FIB-MAA, FIB-CIT, or FIB-MAA-CIT. HFLS-RA cells were stimulated directly with FIB antigens or with …

8 - Training & Exercise, Providence - Special Pathogens Program

Special Pathogens Posters

No abstract provided.

11 - Providence Doffing Room, Providence - Special Pathogens Program

Special Pathogens Posters

No abstract provided.

1 - Special Pathogens Program, Providence - Special Pathogens Program

Special Pathogens Posters

No abstract provided.