The coinhibitory receptor lymphocyte activation gene 3 (LAG-3) is an immune checkpoint molecule that negatively regulates T cell activation, proliferation, and homeostasis. Blockade or deletion of ...LAG-3 in autoimmune-prone backgrounds or induced-disease models has been shown to exacerbate disease. We observed significantly fewer LAG-3
CD4 and CD8 T cells from subjects with relapsing-remitting multiple sclerosis (RRMS) and type 1 diabetes. Low LAG-3 protein expression was linked to alterations in mRNA expression and not cell surface cleavage. Functional studies inhibiting LAG-3 suggest that in subjects with RRMS, LAG-3 retains its ability to suppress T cell proliferation. However, LAG-3 expression was associated with the expression of markers of apoptosis, indicating a role for low LAG-3 in T cell resistance to cell death. In T cells from subjects with RRMS, we observed a global dysregulation of LAG-3 expression stemming from decreased transcription and persisting after T cell stimulation. These findings further support the potential clinical benefits of a LAG-3 agonist in the treatment of human autoimmunity.
OBJECTIVES: To determine the prevalence of chronic pain in elderly people and its relationship with obesity and associated comorbidities and risk factors.
DESIGN: Cross‐sectional.
SETTING: Community.
...PARTICIPANTS: A representative community sample of 840 subjects aged 70 and older.
MEASUREMENTS: The prevalence of chronic pain and its relationship with obesity (categories defined according to body mass index (BMI)), other medical risk factors, and psychiatric comorbidities were examined. Chronic pain was defined as pain of at least moderate severity (≥4 on a 10‐point scale) some, most, or all of the time for the previous 3 months.
RESULTS: The sample was mostly female (62.8%), and the average age was 80 (range 70–101). The prevalence of chronic pain was 52% (39.7% in men; 58.9% in women). Subjects with chronic pain were more likely to report a diagnosis of depression (odds ratio (OR)=2.5, 95% confidence interval (CI)=1.40–4.55) and anxiety (OR=2.3, 95% CI=1.22–4.64). Obese subjects (BMI 30–34.9) were twice as likely (OR=2.1, 95%CI=1.33–3.28) and severely obese subjects (BMI≥35) were more than four times as likely (OR=4.5, 95% CI=1.85–12.63) as those of normal weight (BMI 18.5–24.9) to have chronic pain. Obese subjects were significantly more likely to have chronic pain in the head, neck or shoulder, back, legs or feet, and abdomen or pelvis than subjects who were not obese. In multivariate models, obesity (OR=2.0, 95% CI=1.27–3.26) and severe obesity (OR=4.1, 95% CI=1.57–10.82) were associated with chronic pain after adjusting for age, sex, diabetes mellitus, hypertension, depression, anxiety, and education.
CONCLUSION: Chronic pain is common in this elderly population, affects women more than men, and is highly associated with obesity.
Objective
The objective of this article is to compare acute primary headache patient outcomes in those initially treated with parenteral opiates or non-opiate recommended headache medications in a ...large academic medical emergency department (ED).
Background
Many acute primary headache patients are not diagnosed with a specific headache type and are treated with opiates and nonspecific pain medications in the ED setting. This is inconsistent with multiple expert recommendations.
Methods
Electronic charts were reviewed from 574 consecutive patients who visited the ED for acute primary headache (identified by chief complaint and ICD9 codes) and were treated with parenteral medications.
Results
Non-opiate recommended headache medications were given first line to 52.6% and opiates to 22.8% of all participants. Patients given opiates first had significantly longer length of stays (median 5.0 vs. 3.9 hours, p < 0.001) and higher rates of return ED visits within seven days (7.6% vs. 3.0%, p = 0.033) compared with those given non-opiate recommended medications in univariate analysis. Only the association with longer length of stay remained significant in multivariable regression including possible confounding variables.
Conclusions
Initial opiate use is associated with longer length of stay compared with non-opiate first-line recommended medications for acute primary headache in the ED. This association remained strong and significant even after multivariable adjustment for headache diagnosis and other possible confounders.
Though seemingly counter-intuitive, the violence of enslavement has both sublime and traumatic dimensions that can be considered in relation to Harriet Jacobs's Incidents in the Life of a Slave Girl ...(1861) and Toni Morrison's Beloved (1987). Writing about trauma studies post-9/11, Katharina Donn notes that the sublime "is in all likelihood the most controversial category in scholarly work on trauma, but. . . the aesthetics of the sublime, if demystified and updated, is almost inevitable when trying to understand the relation between mediated spectacle and pain" (26).x While Donn's focus is on the "virtual" trauma of twenty-first century media, especially in relation to 9/11, her point usefully reveals a significant concern of contemporary trauma studies, one yet to be fully explored in older forms of mediation.
Abstract
The intertextual dialogue between the ribbon-kissing scene included in Edith Wharton's The Age of Innocence and Dion Boucicault's two versions of The Shaughraun (as he wrote it and directed ...it) reveals an underexplored dimension of the relationship between Newland Archer and Ellen Olenska. Drawing on Søren Kierkegaard's work, I argue that the conventions of this intertextual scene frame their mutual performance of an implicit angst confined within the constrained social code of the novel's 1870s New York elite. Boucicault's original play did not include the unspoken moment. However, Boucicault added it to capture his audience's interest. The scene presents the attraction between a respectable Englishman and an outlandish Irish woman, with their separation being a consequence of their duties to others, providing a sense of emotional wavering on the edge of dishonor. After both Newland and Ellen connect their relationship to the scene, they repeatedly model it throughout the novel. The conventions of this scene provide a frame for an emotional experience keyed to their social milieu. From this perspective, Newland's retreat at the novel's end may be part of a shared performance with Ellen necessary to realize in the present the angst that would otherwise be lost to memory and history.
The intertextual dialogue between the ribbon-kissing scene included in Edith Wharton's The Age of Innocence and Dion Boucicault's two versions of The Shaughraun (as he wrote it and directed it) ...reveals an underexplored dimension of the relationship between Newland Archer and Ellen Olenska. Drawing on Søren Kierkegaard's work, I argue that the conventions of this intertextual scene frame their mutual performance of an implicit angst confined within the constrained social code of the novel's 1870s New York elite. Boucicault's original play did not include the unspoken moment. However, Boucicault added it to capture his audience's interest. The scene presents the attraction between a respectable Englishman and an outlandish Irish woman, with their separation being a consequence of their duties to others, providing a sense of emotional wavering on the edge of dishonor. After both Newland and Ellen connect their relationship to the scene, they repeatedly model it throughout the novel. The conventions of this scene provide a frame for an emotional experience keyed to their social milieu. From this perspective, Newland's retreat at the novel's end may be part of a shared performance with Ellen necessary to realize in the present the angst that would otherwise be lost to memory and history.
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