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  1. Article ; Online: The Prevalence of Hearing Impairments in Women with Silicone Breast Implants

    Assaf Greenbaum / Gilad Halpert / Arad Dotan / Shaked Shivatzki / Harald Heidecke / Ricky Kaplan Neeman / Michael Ehrenfeld / Amit Wolfovitz / Howard Amital / Yael Henkin / Yehuda Shoenfeld

    Diseases, Vol 11, Iss 31, p

    2023  Volume 31

    Abstract: Many women with silicone breast implants (SBIs) report non-specific complaints, including hearing impairments. Hearing impairment appears to be associated with a number of autoimmune conditions. The current study aimed to evaluate the prevalence and ... ...

    Abstract Many women with silicone breast implants (SBIs) report non-specific complaints, including hearing impairments. Hearing impairment appears to be associated with a number of autoimmune conditions. The current study aimed to evaluate the prevalence and severity of hearing impairments among women with SBIs and to explore potential improvements in their hearing capability following implant removal. Symptomatic women with SBIs ( n = 160) underwent an initial anamnestic interview, and women who reported hearing impairments were selected for the study. These women completed self-report telephone questionnaires regarding their hearing difficulties. Some of these women underwent subjective and objective hearing tests. Out of 159 (50.3%) symptomatic women with SBIs, 80 reported hearing impairments, including hearing loss (44/80; 55%) and tinnitus (45/80; 56.2%). Five out of seven (71.4%) women who underwent an audiologic evaluation exhibited hearing loss. Of women who underwent silicone implant removal, 27 out of 47 (57.4%) reported the improvement or resolution of their hearing complaints. In conclusion, hearing impairment is a frequent complaint among symptomatic women with SBIs, and tinnitus was found to be the most common complaint. A significant reduction in hearing difficulties was observed following silicone implant removal. Further studies using larger populations are needed to verify the occurrence of hearing impairments in these women.
    Keywords silicone breast implants ; hearing impairments ; tinnitus ; autoimmune/inflammatory syndrome induced by adjuvants (ASIA) ; autoimmunity ; autonomic nervous system ; Medicine ; R
    Language English
    Publishing date 2023-02-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: The possible onset of fibromyalgia following acute COVID-19 infection.

    Einat Savin / Gali Rosenn / Avishai M Tsur / Or Hen / Scott Ehrenberg / Omer Gendelman / Dan Buskila / Gilad Halpert / Daniela Amital / Howard Amital

    PLoS ONE, Vol 18, Iss 2, p e

    2023  Volume 0281593

    Abstract: Introduction The exact pathogenesis of fibromyalgia (FM) syndrome is unclear. However, various infectious have been implicated with the development of FM after their acute phase. We aimed to investigate the incidence of FM syndrome among convalesced ... ...

    Abstract Introduction The exact pathogenesis of fibromyalgia (FM) syndrome is unclear. However, various infectious have been implicated with the development of FM after their acute phase. We aimed to investigate the incidence of FM syndrome among convalesced individuals following hospitalization for Acute Coronavirus Disease-2019 (COVID-19). Methods We performed a cross-sectional study on patients who were discharged after COVID-19 hospitalization from the Sheba Medical Center, Israel, between July 2020 to November 2020. A phone interview was performed consisting of the following questionnaires: the Fibromyalgia Survey Diagnostic Criteria Questionnaire, Sense of Coherence Questionnaire to evaluate resilience, and the Subjective Traumatic Outlook Questionnaire to assess the associated psychological aspects of the trauma. The incidence of post-COVID FM was calculated and regression models were performed to identify predictors. Results The study population consisted of 198 eligible patients who completed the phone interview. The median age was 64 (52-72) and 37% were women. The median follow-up was 5.2 months (IQR 4.4-5.8). The incidence of FM was 15% (30 patients) and 87% (172 patients) had at least one FM-related symptom. Female gender was significantly associated with post-COVID FM (OR 3.65, p = 0.002). In addition, high median Subjective Traumatic Outlook scores and low median Sense of Coherence scores were both significantly associated with post-COVID FM (OR 1.19, p<0.001 and OR 0.92, p<0.001, respectively). Conclusions FM is highly prevalent among COVID-19 convalescent patients. Our finding suggests that a significant subjective traumatic experience and a low resilience are highly associated with post-COVID FM.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Functional IgG Autoantibodies against Autonomic Nervous System Receptors in Symptomatic Women with Silicone Breast Implants

    Efrosiniia Talalai / Denis Gorobets / Gilad Halpert / Avishai M. Tsur / Harald Heidecke / Yair Levy / Abdulla Watad / Miri Blank / Izhak Michaelevski / Yehuda Shoenfeld / Howard Amital

    Cells, Vol 12, Iss 1510, p

    2023  Volume 1510

    Abstract: The association between the clinical picture of symptomatic women with silicone breast implants (SBI) and dysregulated immunity was in dispute for decades. In the current study, we describe for the first time the functional activity of purified IgG ... ...

    Abstract The association between the clinical picture of symptomatic women with silicone breast implants (SBI) and dysregulated immunity was in dispute for decades. In the current study, we describe for the first time the functional activity of purified IgG antibodies derived from symptomatic women with SBIs (suffering from subjective/autonomic-related symptoms), both in vitro and in vivo. We found that IgGs, derived from symptomatic women with SBIs, dysregulate inflammatory cytokines (TNFα, IL-6) in activated human peripheral blood mononuclear cells, compared to healthy-women-derived IgGs. Importantly, behavioral studies conducted following intracerebroventricular injection of IgGs derived from symptomatic women with SBIs (who have dysregulated circulating level of IgG autoantibodies directed against autonomic nervous system receptors) into mice brains demonstrated a specific and transient significant increment (about 60%) in the time spent at the center of the open field arena compared with mice injected with IgG from healthy women (without SBIs). This effect was accompanied with a strong trend of reduction of the locomotor activity of the SBI-IgG treated mice, indicating an overall apathic-like behavior. Our study is the first to show the potential pathogenic activity of IgG autoantibodies in symptomatic women with SBIs, emphasizing the importance of these antibodies in SBI-related illness.
    Keywords silicone breast implants ; autoantibodies ; autonomic nervous system ; dysautonomia ; G-protein coupled-receptors ; Biology (General) ; QH301-705.5
    Subject code 150
    Language English
    Publishing date 2023-05-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Immunomodulation of Murine Chronic DSS-Induced Colitis by Tuftsin–Phosphorylcholine

    Dana Ben-Ami Shor / Jordan Lachnish / Tomer Bashi / Shani Dahan / Asaf Shemer / Yahel Segal / Ora Shovman / Gilad Halpert / Alexander Volkov / Iris Barshack / Howard Amital / Miri Blank / Yehuda Shoenfeld

    Journal of Clinical Medicine, Vol 9, Iss 1, p

    2019  Volume 65

    Abstract: Helminths or their products can immunomodulate the host immune system, and this phenomenon may be applied as the basis of new anti-inflammatory treatments. Previously, we have shown the efficacy of tuftsin−phosphorylcholine (TPC), based on a helminth ... ...

    Abstract Helminths or their products can immunomodulate the host immune system, and this phenomenon may be applied as the basis of new anti-inflammatory treatments. Previously, we have shown the efficacy of tuftsin−phosphorylcholine (TPC), based on a helminth product, in four animal models of autoimmune diseases: arthritis, colitis, systemic lupus erythematosus, and experimental autoimmune encephalomyelitis. We demonstrated that TPC reduced inflammatory process ex vivo in peripheral blood lymphocytes (PBLs) and in biopsies from giant-cell arteritis. In the present study, we assessed the therapeutic potential of TPC treatment on a chronic colitis murine model. C57BL/6 mice with chronic colitis were treated with TPC after the third cycle of 2% dextran sodium sulfate (DSS). Oral TPC treatment resulted in amelioration of the colitis clinical manifestations exemplified by reduced disease activity index (DAI) score, expansion of mesenteric lymph nodes (MLN) T regulatory cells (shown by Fluorescence Activated Cell Sorting (FACS)), significant reduction in the expression of pro-inflammatory cytokines (IL-1β, IL17, IL-6, TNFα), and elevation in the expression of anti-inflammatory cytokine IL-10 (shown by RT-PCR). This study demonstrated the potential immunomodulatory effects of oral administration of TPC in a chronic colitis murine model. Further clinical trials are needed in order to evaluate this novel approach for the treatment of patients with inflammatory bowel disease.
    Keywords inflammatory bowel disease ; colitis ; phosphorylcholine ; tuftsin ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2019-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Protein synthesis inhibitor omacetaxine is effective against hepatocellular carcinoma

    Ling Li / Gilad Halpert / Michael G. Lerner / Haijie Hu / Peter Dimitrion / Matthew J. Weiss / Jin He / Benjamin Philosophe / Richard Burkhart / William R. Burns / Russell N. Wesson / Andrew MacGregor Cameron / Christopher L. Wolfgang / Christos Georgiades / Satomi Kawamoto / Nilofer S. Azad / Mark Yarchoan / Stephen J. Meltzer / Kiyoko Oshima /
    Laura M. Ensign / Joel S. Bader / Florin M. Selaru

    JCI Insight, Vol 6, Iss

    2021  Volume 12

    Abstract: Hepatocellular carcinoma (HCC) is the sixth most common and the fourth most deadly cancer worldwide. The development cost of new therapeutics is a major limitation in patient outcomes. Importantly, there is a paucity of preclinical HCC models in which to ...

    Abstract Hepatocellular carcinoma (HCC) is the sixth most common and the fourth most deadly cancer worldwide. The development cost of new therapeutics is a major limitation in patient outcomes. Importantly, there is a paucity of preclinical HCC models in which to test new small molecules. Herein, we implemented potentially novel patient-derived organoid (PDO) and patient-derived xenografts (PDX) strategies for high-throughput drug screening. Omacetaxine, an FDA-approved drug for chronic myelogenous leukemia (CML), was found to be a top effective small molecule in HCC PDOs. Next, omacetaxine was tested against a larger cohort of 40 human HCC PDOs. Serial dilution experiments demonstrated that omacetaxine is effective at low (nanomolar) concentrations. Mechanistic studies established that omacetaxine inhibits global protein synthesis, with a disproportionate effect on short–half-life proteins. High-throughput expression screening identified molecular targets for omacetaxine, including key oncogenes, such as PLK1. In conclusion, by using an innovative strategy, we report — for the first time to our knowledge — the effectiveness of omacetaxine in HCC. In addition, we elucidate key mechanisms of omacetaxine action. Finally, we provide a proof-of-principle basis for future studies applying drug screening PDOs sequenced with candidate validation in PDX models. Clinical trials could be considered to evaluate omacetaxine in patients with HCC.
    Keywords Hepatology ; Oncology ; Medicine ; R
    Subject code 616
    Language English
    Publishing date 2021-06-01T00:00:00Z
    Publisher American Society for Clinical investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Increased protease-activated receptor 1 autoantibodies are associated with severe COVID-19

    Florian Tran / Danielle M.M. Harris / Alena Scharmacher / Hanna Graßhoff / Kristina Sterner / Susanne Schinke / Nadja Käding / Jens Y. Humrich / Otávio Cabral-Marques / Joana P. Bernardes / Neha Mishra / Thomas Bahmer / Jeanette Franzenburg / Bimba F. Hoyer / Andreas Glück / Martina Guggeis / Alexander Ossysek / Andre Küller / Derk Frank /
    Christoph Lange / Jan Rupp / Jan Heyckendorf / Karoline I. Gaede / Howard Amital / Philip Rosenstiel / Yehuda Shoenfeld / Gilad Halpert / Avi Z. Rosenberg / Kai Schulze-Forster / Harald Heidecke / Gabriela Riemekasten / Stefan Schreiber

    ERJ Open Research, Vol 8, Iss

    2022  Volume 4

    Keywords Medicine ; R
    Language English
    Publishing date 2022-12-01T00:00:00Z
    Publisher European Respiratory Society
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article: Local enema treatment to inhibit FOLH1/GCPII as a novel therapy for inflammatory bowel disease

    Date, Abhijit A / Ajit G. Thomas / Alexandra J. Gadiano / Barbara S. Slusher / Gilad Halpert / Jairo Ortiz / Laura M. Ensign / Pranjali Kanvinde / Rana Rais / Sarah C. Zimmermann / Taarika Babu

    Journal of Controlled Release. 2017,

    2017  

    Abstract: Here we evaluate the potential for local administration of a small molecule FOLH1/GCPII inhibitor 2-phosphonomethyl pentanedioic acid (2-PMPA) as a novel treatment for inflammatory bowel disease (IBD). We found that FOLH1/GCPII enzyme activity was ... ...

    Abstract Here we evaluate the potential for local administration of a small molecule FOLH1/GCPII inhibitor 2-phosphonomethyl pentanedioic acid (2-PMPA) as a novel treatment for inflammatory bowel disease (IBD). We found that FOLH1/GCPII enzyme activity was increased in the colorectal tissues of mice with TNBS-induced colitis, and confirmed that 2-PMPA inhibited FOLH1/GCPII enzyme activity ex vivo. In order to maximize local enema delivery of 2-PMPA, we studied the effect of vehicle tonicity on the absorption of 2-PMPA in the colon. Local administration of 2-PMPA in a hypotonic enema vehicle resulted in increased colorectal tissue absorption at 30min compared to 2-PMPA administered in an isotonic enema vehicle. Furthermore, local delivery of 2-PMPA in hypotonic enema vehicle resulted in prolonged drug concentrations for at least 24h with minimal systemic exposure. Finally, daily treatment with the hypotonic 2-PMPA enema ameliorated macroscopic and microscopic symptoms of IBD in the TNBS-induced colitis mouse model, indicating the potential of FOLH1/GCPII inhibitors for the local treatment of IBD.
    Keywords animal models ; colitis ; colon ; drugs ; enzyme activity ; mice ; therapeutics ; tissues
    Language English
    Size p. .
    Publishing place Elsevier B.V.
    Document type Article
    Note Pre-press version
    ZDB-ID 632533-6
    ISSN 1873-4995 ; 0168-3659
    ISSN (online) 1873-4995
    ISSN 0168-3659
    DOI 10.1016/j.jconrel.2017.01.036
    Database NAL-Catalogue (AGRICOLA)

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