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  • 1
    In: Alzheimer's & Dementia, Wiley, Vol. 12, No. 7S_Part_17 ( 2016-07)
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 2201940-6
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  • 2
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Anesthesiology Vol. 127, No. 1 ( 2017-07-01), p. 89-97
    In: Anesthesiology, Ovid Technologies (Wolters Kluwer Health), Vol. 127, No. 1 ( 2017-07-01), p. 89-97
    Abstract: The antifibrinolytic drug tranexamic acid is structurally similar to the amino acid glycine and may cause seizures and myoclonus by acting as a competitive antagonist of glycine receptors. Glycine is an obligatory co-agonist of the N-methyl-d-aspartate (NMDA) subtype of glutamate receptors. Thus, it is plausible that tranexamic acid inhibits NMDA receptors by acting as a competitive antagonist at the glycine binding site. The aim of this study was to determine whether tranexamic acid inhibits NMDA receptors, as well as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate subtypes of ionotropic glutamate receptors. Methods Tranexamic acid modulation of NMDA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and kainate receptors was studied using whole cell voltage-clamp recordings of current from cultured mouse hippocampal neurons. Results Tranexamic acid rapidly and reversibly inhibited NMDA receptors (half maximal inhibitory concentration = 241 ± 45 mM, mean ± SD; 95% CI, 200 to 281; n = 5) and shifted the glycine concentration–response curve for NMDA-evoked current to the right. Tranexamic acid also inhibited α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (half maximal inhibitory concentration = 231 ± 91 mM; 95% CI, 148 to 314; n = 5 to 6) and kainate receptors (half maximal inhibitory concentration = 90 ± 24 mM; 95% CI, 68 to 112; n = 5). Conclusions Tranexamic acid inhibits NMDA receptors likely by reducing the binding of the co-agonist glycine and also inhibits α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate receptors. Receptor blockade occurs at high millimolar concentrations of tranexamic acid, similar to the concentrations that occur after topical application to peripheral tissues. Glutamate receptors in tissues including bone, heart, and nerves play various physiologic roles, and tranexamic acid inhibition of these receptors may contribute to adverse drug effects.
    Type of Medium: Online Resource
    ISSN: 0003-3022
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 2016092-6
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  • 3
    In: Science Advances, American Association for the Advancement of Science (AAAS), Vol. 5, No. 12 ( 2019-12-06)
    Abstract: Sleep disruption is associated with cognitive decline and dementia in older adults; however, the underlying mechanisms are unclear. In rodents, sleep disruption causes microglial activation, inhibition of which improves cognition. However, data from humans are lacking. We studied participants in two cohort studies of older persons—the Rush Memory and Aging Project and the Religious Orders Study. We assessed sleep fragmentation by actigraphy and related this to cognitive function, to neocortical microglial marker gene expression measured by RNA sequencing, and to the neocortical density of microglia assessed by immunohistochemistry. Greater sleep fragmentation was associated with higher neocortical expression of genes characteristic of aged microglia, and a higher proportion of morphologically activated microglia, independent of chronological age- and dementia-related neuropathologies. Furthermore, these were, in turn, associated with worse cognition. This suggests that sleep fragmentation is accompanied by accelerated microglial aging and activation, which may partially underlie its association with cognitive impairment.
    Type of Medium: Online Resource
    ISSN: 2375-2548
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2019
    detail.hit.zdb_id: 2810933-8
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  • 4
    In: Annals of Surgery, Ovid Technologies (Wolters Kluwer Health), Vol. 276, No. 1 ( 2022-07), p. 81-87
    Abstract: The aim of this study was to examine the effect of surgeon-anesthesiologist sex discordance on postoperative outcomes. Summary Background Data: Optimal surgical outcomes depend on teamwork, with surgeons and anesthesiologists forming two key components. There are sex and sex-based differences in interpersonal communication and medical practice which may contribute to patients’ perioperative outcomes. Methods: We performed a population-based, retrospective cohort study among adult patients undergoing 1 of 25 common elective or emergent surgical procedures from 2007 to 2019 in Ontario, Canada. We assessed the association between differences in sex between surgeon and anesthesiologists (sex discordance) on the primary endpoint of adverse postoperative outcome, defined as death, readmission, or complication within 30 days following surgery using generalized estimating equations. Results: Among 1,165,711 patients treated by 3006 surgeons and 1477 anesthesiologists, 791,819 patients were treated by sex concordant teams (male surgeon/male anesthesiologist: 747,327 and female surgeon/female anesthesiologist: 44,492), whereas 373,892 were sex discordant (male surgeon/female anesthesiologist: 267,330 and female surgeon/male anesthesiologist: 106,562). Overall, 12.3% of patients experienced 〉 1 adverse postoperative outcomes of whom 1.3% died. Sex discordance between surgeon and anesthesiologist was not associated with a significant increased likelihood of composite adverse postoperative outcomes (adjusted odds ratio 1.00, 95% confidence interval 0.97–1.03). Conclusions: We did not demonstrate an association between intraoperative surgeon and anesthesiologist sex discordance on adverse postoperative outcomes in a large patient cohort. Patients, clinicians, and administrators may be reassured that physician sex discordance in operating room teams is unlikely to clinically meaningfully affect patient outcomes after surgery.
    Type of Medium: Online Resource
    ISSN: 0003-4932 , 1528-1140
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2641023-0
    detail.hit.zdb_id: 2002200-1
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  • 5
    In: Anesthesiology, Ovid Technologies (Wolters Kluwer Health), Vol. 129, No. 3 ( 2018-09-01), p. 477-489
    Abstract: Postoperative delirium is associated with poor long-term outcomes and increased mortality. General anesthetic drugs may contribute to delirium because they increase cell-surface expression and function of α5 subunit-containing γ-aminobutyric acid type A receptors, an effect that persists long after the drugs have been eliminated. Dexmedetomidine, an α2 adrenergic receptor agonist, prevents delirium in patients and reduces cognitive deficits in animals. Thus, it was postulated that dexmedetomidine prevents excessive function of α5 γ-aminobutyric acid type A receptors. Methods Injectable (etomidate) and inhaled (sevoflurane) anesthetic drugs were studied using cultured murine hippocampal neurons, cultured murine and human cortical astrocytes, and ex vivo murine hippocampal slices. γ-Aminobutyric acid type A receptor function and cell-signaling pathways were studied using electrophysiologic and biochemical methods. Memory and problem-solving behaviors were also studied. Results The etomidate-induced sustained increase in α5 γ-aminobutyric acid type A receptor cell-surface expression was reduced by dexmedetomidine (mean ± SD, etomidate: 146.4 ± 51.6% vs. etomidate + dexmedetomidine: 118.4 ± 39.1% of control, n = 8 each). Dexmedetomidine also reduced the persistent increase in tonic inhibitory current in hippocampal neurons (etomidate: 1.44 ± 0.33 pA/pF, n = 10; etomidate + dexmedetomidine: 1.01 ± 0.45 pA/pF, n = 9). Similarly, dexmedetomidine prevented a sevoflurane-induced increase in the tonic current. Dexmedetomidine stimulated astrocytes to release brain-derived neurotrophic factor, which acted as a paracrine factor to reduce excessive α5 γ-aminobutyric acid type A receptor function in neurons. Finally, dexmedetomidine attenuated memory and problem-solving deficits after anesthesia. Conclusions Dexmedetomidine prevented excessive α5 γ-aminobutyric acid type A receptor function after anesthesia. This novel α2 adrenergic receptor- and brain-derived neurotrophic factor-dependent pathway may be targeted to prevent delirium.
    Type of Medium: Online Resource
    ISSN: 0003-3022
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 2016092-6
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  • 6
    In: JAMA Surgery, American Medical Association (AMA)
    Abstract: Sex- and gender-based differences in a surgeon’s medical practice and communication may be factors in patients’ perioperative outcomes. Patients treated by female surgeons have improved 30-day outcomes. However, whether these outcomes persist over longer follow-up has not been assessed. Objective To examine whether surgeon sex is associated with 90-day and 1-year outcomes among patients undergoing common surgeries. Design, Setting, and Participants A population-based retrospective cohort study was conducted in adults in Ontario, Canada, undergoing 1 of 25 common elective or emergent surgeries between January 1, 2007, and December 31, 2019. Analysis was performed between July 15 and October 20, 2022. Exposure Surgeon sex. Main Outcomes and Measures An adverse postoperative event, defined as the composite of death, readmission, or complication, was assessed at 90 days and 1 year following surgery. Secondarily, each of these outcomes was assessed individually. Outcomes were compared between patients treated by female and male surgeons using generalized estimating equations with clustering at the level of the surgical procedure, accounting for patient-, procedure-, surgeon-, anesthesiologist-, and facility-level covariates. Results Among 1 165 711 included patients, 151 054 were treated by a female and 1 014 657 by a male surgeon. Overall, 14.3% of the patients had 1 or more adverse postoperative outcomes at 90 days and 25.0% had 1 or more adverse postoperative outcomes 1 year following surgery. Among these, 2.0% of patients died within 90 days and 4.3% died within 1 year. Multivariable-adjusted rates of the composite end point were higher among patients treated by male than female surgeons at both 90 days (13.9% vs 12.5%; adjusted odds ratio [AOR], 1.08; 95% CI, 1.03-1.13) and 1 year (25.0% vs 20.7%; AOR, 1.06; 95% CI, 1.01-1.12). Similar patterns were observed for mortality at 90 days (0.8% vs 0.5%; AOR 1.25; 95% CI, 1.12-1.39) and 1 year (2.4% vs 1.6%; AOR, 1.24; 95% CI, 1.13-1.36). Conclusions and Relevance After accounting for patient, procedure, surgeon, anesthesiologist, and hospital characteristics, the findings of this cohort study suggest that patients treated by female surgeons have lower rates of adverse postoperative outcomes including death at 90 days and 1 year after surgery compared with those treated by male surgeons. These findings further support differences in patient outcomes based on physician sex that warrant deeper study regarding underlying causes and potential solutions.
    Type of Medium: Online Resource
    ISSN: 2168-6254
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
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