Variation in plasma levels of cortisol, an essential hormone in the stress response, is associated in population-based studies with cardio-metabolic, inflammatory and neuro-cognitive traits and diseases. Heritability of plasma cortisol is estimated at 30–60% but no common genetic contribution has been identified. The CORtisol NETwork (CORNET) consortium undertook genome wide association meta-analysis for plasma cortisol in 12,597 Caucasian participants, replicated in 2,795 participants. The results indicate that <1% of variance in plasma cortisol is accounted for by genetic variation in a single region of chromosome 14. This locus spans SERPINA6, encoding corticosteroid binding globulin (CBG, the major cortisol-binding protein in plasma), and SERPINA1, encoding α1-antitrypsin (which inhibits cleavage of the reactive centre loop that releases cortisol from CBG). Three partially independent signals were identified within the region, represented by common SNPs; detailed biochemical investigation in a nested sub-cohort showed all these SNPs were associated with variation in total cortisol binding activity in plasma, but some variants influenced total CBG concentrations while the top hit (rs12589136) influenced the immunoreactivity of the reactive centre loop of CBG. Exome chip and 1000 Genomes imputation analysis of this locus in the CROATIA-Korcula cohort identified missense mutations in SERPINA6 and SERPINA1 that did not account for the effects of common variants. These findings reveal a novel common genetic source of variation in binding of cortisol by CBG, and reinforce the key role of CBG in determining plasma cortisol levels. In turn this genetic variation may contribute to cortisol-associated degenerative diseases.

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IMPORTANCEThe association of COVID-19 not requiring hospitalization with functional mobility in community-dwelling adults above and beyond the impact of the pandemic control measures implemented in 2020 remains to be elucidated. OBJECTIVETo evaluate the association between a COVID-19 diagnosis and change in mobility and physical function of adults in Canada aged 50 years or older during the initial pandemic lockdown. DESIGN, SETTING, AND PARTICIPANTS This population-based cohort study used data from the Canadian Longitudinal Study on Aging (CLSA) COVID-19 study. This study was launched on April 15, 2020, and the exit questionnaires were completed between September and December 2020. Prepandemic data from the first CLSA follow-up (2015-2018) were also used. Respondents included middle-aged and older community-dwelling participants residing in Canadian provinces. Data were analyzed from February to May 2021. EXPOSURES The assessment for self-reported COVID-19 status was adapted from the Public Health Agency of Canada and the Centers for Disease Control and Prevention case definition available at the time of data collection; cases were classified as confirmed or probable, suspected, or non-COVID-19. MAIN OUTCOMES AND MEASURES Changes in mobility since the start of the COVID-19 pandemic were assessed using global rating of change in mobility scales at the COVID-19 exit questionnaire.Participant-reported new onset of difficulty in 3 physical function tasks was also examined. RESULTS Among 51 338 participants at baseline, 21 491 participants (41.9%) were 65 years or older and 26 155 participants (51.0%) were women and 25 183 (49.1%) were men. Of 2748 individuals with confirmed or probable or suspected 113 (94.2%) were not hospitalized. Individuals with confirmed or probable COVID-19 had higher odds of worsening mobility in terms of ability to engage in household activity (odds ratio [OR], 1.89; 95% CI, 1.11-3.22), physical activity (OR, 1.91; 95% CI, 1.32-2.76), and standing up after sitting in a chair (OR, 2.33; 95% CI, 1.06-5.11) compared with adults without COVID-19 during the same pandemic time period. Similar results were found for suspected COVID-19 status (eg, household activity: OR, 2.09; 95% CI, 1.82-2.41). CONCLUSIONS AND RELEVANCEThis cohort study among older adults in Canada found that receiving a COVID-19 diagnosis was significantly associated with worse mobility and functioning outcomes even in the absence of hospitalization. These findings suggest that interventions may be needed for individuals with mild to moderate COVID-19 who do not require hospitalization.

Redundant mechanisms underlie homing of leukocytes to the uterus and their importance can be evaluated by an in vivo approach described herein.

Background: Psychiatric patients experience longer treatment times (length of stay [LOS]) in the emergency department (ED) compared to nonpsychiatric patients. Although patients on involuntary mental health holds are relatively understudied, common wisdom would hold that times for these patients can only be affected by addressing systems issues because they are not free to leave. The objective of this study was to determine whether both selected ED and patient-specific factors were associated with longer LOS. We hypothesized that nonmodifiable factors (age, sex, agitation, presentation during evenings/nights, presentation during weekends, suicidal ideation) would prolong LOS but that potentially modifiable factors (such as use of medication) would reduce LOS. Methods: A historical cohort of patients (January 1, 2009-August 16, 2010) placed on involuntary mental health holds was studied in 2 general EDs. A regression model was used to calculate the effects of modifiable and nonmodifiable factors on LOS. Results: Six hundred forty patient visits met all inclusion/exclusion criteria. Longer LOSs were significantly associated with suicidal ideation, use of antipsychotics, and use of benzodiazepines, although agitation did not predict longer LOSs. Longer LOSs were also longer with presentation on the weekends. Conclusions: Lengths of stay for patients on involuntary mental health holds are associated with several factors outside the control of the typical ED clinician such as the ability to clear holds quickly due to day of week or placement of the hold for suicidal ideation. Lengths of stay are also increased by factors within the control of the typical ED clinician, such as administration of calming medication.