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  1. Article ; Online: Post-partum female who woke up with hemiparesis.

    Wira, Charles R / Marcolini, Evie / Bulsara, Ketan R

    Journal of the American College of Emergency Physicians open

    2022  Volume 3, Issue 5, Page(s) e12807

    Language English
    Publishing date 2022-09-05
    Publishing country United States
    Document type Journal Article
    ISSN 2688-1152
    ISSN (online) 2688-1152
    DOI 10.1002/emp2.12807
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  2. Article ; Online: The Future of Minor Stroke and Transient Ischemic Attack: The RAVEN Approach Is Promising but Not Ready for Prime Time.

    Madsen, Tracy E / Wira, Charles R

    Annals of emergency medicine

    2019  Volume 74, Issue 4, Page(s) 572–574

    MeSH term(s) Animals ; Crows ; Feasibility Studies ; Humans ; Ischemic Attack, Transient ; Neurology ; Outpatients ; Stroke
    Language English
    Publishing date 2019-09-22
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 603080-4
    ISSN 1097-6760 ; 0196-0644
    ISSN (online) 1097-6760
    ISSN 0196-0644
    DOI 10.1016/j.annemergmed.2019.08.458
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  3. Article: Aging beyond menopause selectively decreases CD8+ T cell numbers but enhances cytotoxic activity in the human endometrium.

    Shen, Zheng / Patel, Mickey V / Rodriguez-Garcia, Marta / Wira, Charles R

    Immunity & ageing : I & A

    2022  Volume 19, Issue 1, Page(s) 55

    Abstract: Background: Regulation of endometrial (EM) CD8+ T cells, which provide protection through cell-mediated cytotoxicity, is essential for successful reproduction, and protection against sexually transmitted infections and potential tumors. We have ... ...

    Abstract Background: Regulation of endometrial (EM) CD8+ T cells, which provide protection through cell-mediated cytotoxicity, is essential for successful reproduction, and protection against sexually transmitted infections and potential tumors. We have previously demonstrated that EM CD8+ T cell cytotoxicity is suppressed directly and indirectly by sex hormones and enhanced after menopause. What remains unclear is whether CD8+ T cell protection and the contribution of tissue-resident (CD103+) and non-resident (CD103-) T cell populations in the EM change as women age following menopause.
    Results: Using hysterectomy EM tissues, we found that EM CD8+ T cell numbers declined significantly in the years following menopause. Despite an overall decline in CD8+ T cells, cytotoxic activity per cell for both CD103- and CD103 + CD8+ T cells increased with age. Investigation of the underlying mechanisms responsible for cytotoxicity indicated that the percentage of total granzyme A and granzyme B positive CD8+ T cells, but not perforin, increased significantly after menopause and remained high and constant as women aged. Additionally, baseline TNFα production by EM CD8+ T cells increased significantly in the years following menopause, and estradiol suppressed TNFα secretion. Moreover, in response to PMA activation, TNFα and IFNγ were significantly up-regulated, and CD103-CD8+ T cells up-regulation of TNFα, IFNγ and IL-6 increased as women aged.
    Conclusions: Understanding the underlying factors involved in regulating cell-mediated protection of the EM by CD8+ T cells will contribute to the foundation of information essential for developing therapeutic tools to protect women against gynecological cancers and infections as they age.
    Language English
    Publishing date 2022-11-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 2168941-6
    ISSN 1742-4933
    ISSN 1742-4933
    DOI 10.1186/s12979-022-00312-w
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  4. Article ; Online: Sex Hormones and Aging Modulate Interferon Lambda 1 Production and Signaling by Human Uterine Epithelial Cells and Fibroblasts.

    Patel, Mickey V / Hopkins, Daniel C / Barr, Fiona D / Wira, Charles R

    Frontiers in immunology

    2021  Volume 12, Page(s) 718380

    Abstract: Estradiol ( ... ...

    Abstract Estradiol (E
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Aging/genetics ; Aging/metabolism ; Cell Line ; Cells, Cultured ; Cytokines/metabolism ; Endometrium/cytology ; Endometrium/metabolism ; Epithelial Cells/metabolism ; Estradiol/metabolism ; Female ; Fibroblasts/metabolism ; Gonadal Steroid Hormones/metabolism ; Humans ; Interferons/biosynthesis ; Interleukins/biosynthesis ; Middle Aged ; Progesterone/metabolism ; Signal Transduction
    Chemical Substances Cytokines ; Gonadal Steroid Hormones ; interferon-lambda, human ; Interleukins ; Progesterone (4G7DS2Q64Y) ; Estradiol (4TI98Z838E) ; Interferons (9008-11-1)
    Language English
    Publishing date 2021-09-24
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.718380
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  5. Article ; Online: Medroxyprogesterone acetate inhibits wound closure of human endometrial epithelial cells and stromal fibroblasts in vitro.

    Patel, Mickey V / Rodriguez-Garcia, Marta / Shen, Zheng / Wira, Charles R

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 23246

    Abstract: Mucosal integrity in the endometrium is essential for immune protection. Since breaches or injury to the epithelial barrier exposes underlying tissue and is hypothesized to increase infection risk, we determined whether endogenous progesterone or three ... ...

    Abstract Mucosal integrity in the endometrium is essential for immune protection. Since breaches or injury to the epithelial barrier exposes underlying tissue and is hypothesized to increase infection risk, we determined whether endogenous progesterone or three exogenous progestins (medroxyprogesterone acetate (MPA), norethindrone (NET), and levonorgestrel (LNG)) used by women as contraceptives interfere with wound closure of endometrial epithelial cells and fibroblasts in vitro. Progesterone and LNG had no inhibitory effect on wound closure by either epithelial cells or fibroblasts. MPA significantly impaired wound closure in both cell types and delayed the reestablishment of transepithelial resistance by epithelial cells. In contrast to MPA, NET selectively decreased wound closure by stromal fibroblasts but not epithelial cells. Following epithelial injury, MPA but not LNG or NET, blocked the injury-induced upregulation of HBD2, a broad-spectrum antimicrobial implicated in wound healing, but had no effect on the secretion of RANTES, CCL20 and SDF-1α. This study demonstrates that, unlike progesterone and LNG, MPA and NET may interfere with wound closure following injury in the endometrium, potentially conferring a higher risk of pathogen transmission. Our findings highlight the importance of evaluating progestins for their impact on wound repair at mucosal surfaces.
    MeSH term(s) Adult ; Cells, Cultured ; Contraceptive Agents/pharmacology ; Endometrium/drug effects ; Endometrium/injuries ; Epithelial Cells/drug effects ; Female ; Fibroblasts/drug effects ; Humans ; Levonorgestrel/pharmacology ; Medroxyprogesterone Acetate/pharmacology ; Middle Aged ; Norethindrone/pharmacology ; Progesterone/pharmacology ; Wound Healing/drug effects
    Chemical Substances Contraceptive Agents ; Progesterone (4G7DS2Q64Y) ; Levonorgestrel (5W7SIA7YZW) ; Medroxyprogesterone Acetate (C2QI4IOI2G) ; Norethindrone (T18F433X4S)
    Language English
    Publishing date 2021-12-01
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-02681-6
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  6. Article ; Online: The impact of aging on innate and adaptive immunity in the human female genital tract.

    Rodriguez-Garcia, Marta / Patel, Mickey V / Shen, Zheng / Wira, Charles R

    Aging cell

    2021  Volume 20, Issue 5, Page(s) e13361

    Abstract: Mucosal tissues in the human female reproductive tract (FRT) are primary sites for both gynecological cancers and infections by a spectrum of sexually transmitted pathogens, including human immunodeficiency virus (HIV), that compromise women's health. ... ...

    Abstract Mucosal tissues in the human female reproductive tract (FRT) are primary sites for both gynecological cancers and infections by a spectrum of sexually transmitted pathogens, including human immunodeficiency virus (HIV), that compromise women's health. While the regulation of innate and adaptive immune protection in the FRT by hormonal cyclic changes across the menstrual cycle and pregnancy are being intensely studied, little to nothing is known about the alterations in mucosal immune protection that occur throughout the FRT as women age following menopause. The immune system in the FRT has two key functions: defense against pathogens and reproduction. After menopause, natural reproductive function ends, and therefore, two overlapping processes contribute to alterations in immune protection in aging women: menopause and immunosenescence. The goal of this review is to summarize the multiple immune changes that occur in the FRT with aging, including the impact on the function of epithelial cells, immune cells, and stromal fibroblasts. These studies indicate that major aspects of innate and adaptive immunity in the FRT are compromised in a site-specific manner in the FRT as women age. Further, at some FRT sites, immunological compensation occurs. Overall, alterations in mucosal immune protection contribute to the increased risk of sexually transmitted infections (STI), urogenital infections, and gynecological cancers. Further studies are essential to provide a foundation for the development of novel therapeutic interventions to restore immune protection and reverse conditions that threaten women's lives as they age.
    MeSH term(s) Adaptive Immunity ; Aging/immunology ; Epithelial Cells/physiology ; Female ; Fibroblasts/physiology ; Genital Neoplasms, Female/etiology ; Genitalia, Female/immunology ; Genitalia, Female/physiology ; Humans ; Immunity, Innate ; Macrophages/immunology ; Menopause ; Reproductive Tract Infections/etiology ; T-Lymphocytes/immunology
    Language English
    Publishing date 2021-05-05
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2113083-8
    ISSN 1474-9726 ; 1474-9718
    ISSN (online) 1474-9726
    ISSN 1474-9718
    DOI 10.1111/acel.13361
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6581: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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  7. Article ; Online: Composition of the Sepsis Definitions Task Force.

    Wira, Charles R / Swenson, Kai E

    JAMA

    2016  Volume 316, Issue 4, Page(s) 460

    MeSH term(s) Humans ; Organ Dysfunction Scores ; Sepsis/diagnosis
    Language English
    Publishing date 2016-07-26
    Publishing country United States
    Document type Comment ; Letter
    ZDB-ID 2958-0
    ISSN 1538-3598 ; 0254-9077 ; 0002-9955 ; 0098-7484
    ISSN (online) 1538-3598
    ISSN 0254-9077 ; 0002-9955 ; 0098-7484
    DOI 10.1001/jama.2016.6371
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    Ua VI Zs.88: Show issues Location:
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  8. Article: Aging modifies endometrial dendritic cell function and unconventional double negative T cells in the human genital mucosa.

    Parthasarathy, Siddharth / Shen, Zheng / Carrillo-Salinas, Francisco J / Iyer, Vidya / Vogell, Alison / Illanes, Diego / Wira, Charles R / Rodriguez-Garcia, Marta

    Immunity & ageing : I & A

    2023  Volume 20, Issue 1, Page(s) 34

    Abstract: Background: Immune function in the genital mucosa balances reproduction with protection against pathogens. As women age, genital infections, and gynecological cancer risk increase, however, the mechanisms that regulate cell-mediated immune protection in ...

    Abstract Background: Immune function in the genital mucosa balances reproduction with protection against pathogens. As women age, genital infections, and gynecological cancer risk increase, however, the mechanisms that regulate cell-mediated immune protection in the female genital tract and how they change with aging remain poorly understood. Unconventional double negative (DN) T cells (TCRαβ + CD4-CD8-) are thought to play important roles in reproduction in mice but have yet to be characterized in the human female genital tract. Using genital tissues from women (27-77 years old), here we investigated the impact of aging on the induction, distribution, and function of DN T cells throughout the female genital tract.
    Results: We discovered a novel site-specific regulation of dendritic cells (DCs) and unconventional DN T cells in the genital tract that changes with age. Human genital DCs, particularly CD1a + DCs, induced proliferation of DN T cells in a TFGβ dependent manner. Importantly, induction of DN T cell proliferation, as well as specific changes in cytokine production, was enhanced in DCs from older women, indicating subset-specific regulation of DC function with increasing age. In human genital tissues, DN T cells represented a discrete T cell subset with distinct phenotypical and transcriptional profiles compared to CD4 + and CD8 + T cells. Single-cell RNA and oligo-tag antibody sequencing studies revealed that DN T cells represented a heterogeneous population with unique homeostatic, regulatory, cytotoxic, and antiviral functions. DN T cells showed relative to CD4 + and CD8 + T cells, enhanced expression of inhibitory checkpoint molecules and genes related to immune regulatory as well as innate-like anti-viral pathways. Flow cytometry analysis demonstrated that DN T cells express tissue residency markers and intracellular content of cytotoxic molecules. Interestingly, we demonstrate age-dependent and site-dependent redistribution and functional changes of genital DN T cells, with increased cytotoxic potential of endometrial DN T cells, but decreased cytotoxicity in the ectocervix as women age, with implications for reproductive failure and enhanced susceptibility to infections respectively.
    Conclusions: Our deep characterization of DN T cell induction and function in the female genital tract provides novel mechanistic avenues to improve reproductive outcomes, protection against infections and gynecological cancers as women age.
    Language English
    Publishing date 2023-07-14
    Publishing country England
    Document type Journal Article
    ZDB-ID 2168941-6
    ISSN 1742-4933
    ISSN 1742-4933
    DOI 10.1186/s12979-023-00360-w
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  9. Article ; Online: Diagnosis, Workup, Risk Reduction of Transient Ischemic Attack in the Emergency Department Setting: A Scientific Statement From the American Heart Association.

    Amin, Hardik P / Madsen, Tracy E / Bravata, Dawn M / Wira, Charles R / Johnston, S Claiborne / Ashcraft, Susan / Burrus, Tamika M / Panagos, Peter D / Wintermark, Max / Esenwa, Charles

    Stroke

    2023  Volume 54, Issue 3, Page(s) e109–e121

    Abstract: At least 240 000 individuals experience a transient ischemic attack each year in the United States. Transient ischemic attack is a strong predictor of subsequent stroke. The 90-day stroke risk after transient ischemic attack can be as high as 17.8%, with ...

    Abstract At least 240 000 individuals experience a transient ischemic attack each year in the United States. Transient ischemic attack is a strong predictor of subsequent stroke. The 90-day stroke risk after transient ischemic attack can be as high as 17.8%, with almost half occurring within 2 days of the index event. Diagnosing transient ischemic attack can also be challenging given the transitory nature of symptoms, often reassuring neurological examination at the time of evaluation, and lack of confirmatory testing. Limited resources, such as imaging availability and access to specialists, can further exacerbate this challenge. This scientific statement focuses on the correct clinical diagnosis, risk assessment, and management decisions of patients with suspected transient ischemic attack. Identification of high-risk patients can be achieved through use of comprehensive protocols incorporating acute phase imaging of both the brain and cerebral vasculature, thoughtful use of risk stratification scales, and ancillary testing with the ultimate goal of determining who can be safely discharged home from the emergency department versus admitted to the hospital. We discuss various methods for rapid yet comprehensive evaluations, keeping resource-limited sites in mind. In addition, we discuss strategies for secondary prevention of future cerebrovascular events using maximal medical therapy and patient education.
    MeSH term(s) Humans ; United States ; Ischemic Attack, Transient/diagnosis ; Ischemic Attack, Transient/therapy ; Ischemic Attack, Transient/complications ; American Heart Association ; Stroke/diagnosis ; Stroke/prevention & control ; Emergency Service, Hospital ; Risk Reduction Behavior
    Language English
    Publishing date 2023-01-19
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 80381-9
    ISSN 1524-4628 ; 0039-2499 ; 0749-7954
    ISSN (online) 1524-4628
    ISSN 0039-2499 ; 0749-7954
    DOI 10.1161/STR.0000000000000418
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    Zs.A 448: Show issues Location:
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  10. Article ; Online: Cause of an Elevated Lactate Level.

    Swenson, Kai E / Wira, Charles R

    JAMA

    2015  Volume 313, Issue 23, Page(s) 2381

    MeSH term(s) Acidosis, Lactic/etiology ; Humans ; Lactates/blood ; Lymphoma/diagnosis ; Male
    Chemical Substances Lactates
    Language English
    Publishing date 2015-06-16
    Publishing country United States
    Document type Comment ; Letter
    ZDB-ID 2958-0
    ISSN 1538-3598 ; 0254-9077 ; 0002-9955 ; 0098-7484
    ISSN (online) 1538-3598
    ISSN 0254-9077 ; 0002-9955 ; 0098-7484
    DOI 10.1001/jama.2015.5043
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    Ua VI Zs.88: Show issues Location:
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