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- Dahlqvist, Martin, et al.
(författare)
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Complex magnetism in nanolaminated Mn2GaC
- 2014
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We have used first-principles calculations and Heisenberg Monte Carlo simulations to search for the magnetic ground state of Mn2GaC, a recently synthesized magnetic nanolaminate. We have, independent on method, identified a range of low energy collinear as well as non-collinear magnetic configurations, indicating a highly frustrated magnetic material with several nearly degenerate magnetic states. An experimentally obtained magnetization of only 0.29 per Mn atom in Mn2GaC may be explained by canted spins in an antiferromagnetic configuration of ferromagnetically ordered sub-layers with alternating spin orientation, denoted AFM[0001]. Furthermore, low temperature X-ray diffraction show a new basal plane peak appearing upon a magnetic transition, which is consistent with the here predicted change in inter-layer spacing for the AFM[0001] configuration.
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| 4. |
- Brorsson, Camilla, et al.
(författare)
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Liver resection is not associated with decreased cortisol levels.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Adrenal hormones are synthesized from cholesterol, produced and stored in the liver. Liver failure has been reported to be associated with adrenal insufficiency. A possible mechanism could be a limited supply of substrate for cortisol synthesis. The aims of this study was to evaluate the occurrence of total serum cortisol <200 nmol/L after major liver resection (≥ 30%) and other major surgery (hemicolectomy) and to assess associations between cholesterol and cortisol levels after liver resection.Methods: Prospective, observational study. 40 patients were included (major liver resection n=15, hemicolectomy n=25). Serum and salivary cortisol were followed from morning before surgery up to five days postoperatively. Sulphated dehydroepiandrosterone (DHEAS) and lipids (cholesterol, low density lipoproteins, high density lipoproteins and triglycerides) were obtained in liver resection patients.Results: 8/25 (32%, hemicolectomy patients), and 3/15 (20%, liver resection patients) had serum cortisol <200 nmol/L. Neither hemicolectomy nor liver resection was significantly associated with serum cortisol <200 nmol/L, p=0.49. Serum cortisol <200 nmol/L was not significantly associated with lipids below normal limits, (cholesterol; p=1.0 day 1, p=0.46 day 4, LDL; p=0.56 day 1, p=1.0 day 4, and HDL; p=0.27 day 1, p=1.0 day 4). Serum and salivary cortisol correlated significantly (rs=0.83, p<0.0001, hemicolectomy, rs=0.80, p<0.0001, liver resection).Conclusion: Serum cortisol levels <200 nmol/L was found in 32% (hemicolectomy) and 20% (liver resection) postoperatively. Compared to after hemicolectomy, serum cortisol <200 nmol/L was not significantly more common after liver resection. Lipids below normal limits were not associated with serum cortisol <200 nmol/L after liver resection.
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- Brorsson, Camilla, 1967-
(författare)
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Trauma - logistics and stress response
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Trauma is a major cause of death and disability. Adverse events, such as prolonged prehospital time, hypoxia, hypotension and/or hyperventilation have been reported to correlate to poor outcome.Adequate cortisol levels are essential for survival after major trauma. In hypotensive critically ill patients, lack of sufficient amount of cortisol can be suspected, and a concept of critical illness related corticosteroid insufficiency has been proposed. Corticosteroid therapy has many adverse effects in critically ill patients and should only be given if life-saving. Correct measurement of serum cortisol levels is important but difficult in critically ill patients with capillary leakage. Estimation of the free and biologically active cortisol is preferable. In serum less than 10% of cortisol is free and biologically active and not possible to measure with routine laboratory methods. Salivary cortisol can be used as a surrogate for free cortisol, but salivary production is reduced in critically ill patients. Liver resection could reduce cortisol levels due to substrate deficiency.Aims: 1. Evaluate the occurrence of early adverse events in patients with traumatic brain injury and relate them to outcome. 2. Assess cortisol levels over time after trauma and correlate to severity of trauma, sedative/analgesic drugs and cardiovascular function. 3. Evaluate if saliva stimulation could be performed without interfering with salivary cortisol levels. 4. Assess cortisol levels over time after liver resection in comparison to other major surgery.Results: There was no significant correlation between prehospital time ³60 minutes, hypoxia (saturation <95%), hypotension (systolic blood pressure <90 mmHg), or hyperventilation (ETCO2 <4.5 kPa) and a poor outcome (Glasgow Outcome Scale 1-3) in patients with traumatic brain injury. Cortisol levels decreased significantly over time after trauma, but there was no correlation between low (<200 nmol/L) serum cortisol levels and severity of trauma.Infusion of sedative/analgesic drugs was the strongest predictor for a low (<200 nmol/L) serum cortisol. The odds ratio for low serum cortisol levels (<200 nmol/L) was 8.0 for patients receiving continuous infusion of sedative/analgesic drugs. There was no significant difference between unstimulated and stimulated salivary cortisol levels (p=0.06) in healthy volunteers. Liver resection was not associated with significantly lower cortisol levels compared to other major surgery.Conclusion: There was no significant correlation between early adverse events and outcome in patients with traumatic brain injury. Cortisol levels decreased significantly over time in trauma patients. Low cortisol levels (<200 nmol/L) were significantly correlated to continuous infusion of sedative/analgesic drugs. Saliva stimulation could be performed without interfering with salivary cortisol levels. Liver resection was not associated with low cortisol levels compared to other major surgery.
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| 8. |
- Bäcklund, Nils, 1987-
(författare)
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Diagnosing hyper- and hypocortisolism using saliva samples : pitfalls and how to avoid them
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Cushing's syndrome (CS) is caused by high cortisol secretion whereas insufficient cortisol secretion is called adrenal insufficiency (AI). Both are rare diseases with substantial diagnostic delay, and high morbidity and mortality even though effective treatment is available. This thesis aims to improve diagnostic tests for CS and AI using analyses of cortisol and its inactive metabolite cortisone in saliva samples.Methods: Papers 1 and 2 are based on a reference cohort including 155 individuals and 22 patients with CS. Salivary samples were collected at late-night (23:00 hours ± 15 minutes) and after a 1-mg overnight dexamethasone suppression test (DST). In Paper 1, reference intervals for salivary cortisol and cortisone analyzed with liquid chromatography-tandem mass spectrometry (LC-MS/MS) were established for late-night and post-DST samples. Diagnostic accuracy for CS was calculated using the established reference intervals. Potential effects of age, comorbidities, season, and sampling time point were also studied. In Paper 2, different analytical methods for measurement of salivary cortisol (3 LC-MS/MS and 3 immunoassays) and salivary cortisone (3 LC-MS/MS assays) were compared regarding reference intervals and diagnostic accuracies for CS. Paper 3 elucidated the potential effect of liquorice consumption, blood contamination, and topical hydrocortisone handling prior to sampling on salivary cortisol and cortisone. Paper 4 investigated whether salivary cortisol and cortisone are less affected than plasma cortisol by estrogen-containing oral contraceptive (OCs) in women undergoing a short Synacthen test (SST) by comparing the response in women with (n=41) and without OCs (n=46).Results: Paper 1 established reference intervals for salivary cortisol and cortisone at 23:00 hours and after DST. Using the upper reference limits as cut-offs, the diagnostic tests rendered high diagnostic accuracy for CS using salivary cortisol (sensitivity 90–95 %, specificity 96 %). There was no seasonal variation and no significant difference between samples collected at 22:00 vs 23:00 hours. Salivary cortisone showed a higher diagnostic accuracy for CS (sensitivity 100 % and specificity 94–95 %) and was less affected by other comorbidities compared to salivary cortisol. Paper 2 showed very high agreement between the three LC-MS/MS methods and that measuring salivary cortisol with immunoassays resulted in higher cortisol concentrations than with LC-MS/MS. However, using the newly established reference limits for each method, all had high diagnostic accuracy for CS. Late-night salivary cortisone analyzed with the LC-MS/MS methods and salivary cortisol analyzed with the Roche immunoassay showed the highest diagnostic accuracies. Paper 3 showed that liquorice consumption increased late-night salivary cortisol, which was sustained for up to 6 days, whereas no effect was seen on salivary cortisone. Salivary cortisol, but not cortisone, was increased by contamination of saliva with ≥0.5 % blood, which could be revealed by a clearly visible red discoloration of the saliva. Handling of topical hydrocortisone before saliva sampling affected salivary cortisol to a much higher degree than salivary cortisone. Paper 4 showed that women using OCs have considerably higher plasma cortisol levels during an SST, whereas salivary cortisol and salivary cortisone were lower compared to controls. However, the lower reference limits were not significantly different for salivary measurands, with salivary cortisone slightly more robust, opting for a common cut-off to exclude AI regardless of OCs.Conclusion: Using the reference intervals calculated for several clinically used analytical methods showed high diagnostic accuracy for CS, with cortisone showing the highest accuracy. Analyzing salivary cortisone was not affected by liquorice consumption or blood contamination. Salivary cortisone was least affected by OCs during an SST. In summary, salivary cortisone is very useful in the diagnostic work-up for CS and AI.
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- Consiglio, Camila, et al.
(författare)
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Immune system adaptation during gender-affirming testosterone treatment
- 2023
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Ingår i: Journal of Reproductive Immunology. - : Elsevier. - 0165-0378 .- 1872-7603. ; 159, s. 29-30
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Biological sex impacts human immune responses, modulating susceptibility and severity to immune-related diseases. Female generally mount more robust immune responses than males, resulting in lower infection severity and greater autoimmunity incidence. Here, we addressed the contribution of testosterone to human immune function by analyzing a cohort of subjects undergoing gender-affirming testosterone treatment. We performed systems-level immunomonitoring through mass cytometry, scRNA and scA-TAC-Sequencing, and proteome profiling of blood samples at baseline and following 3 and 12 months of treatment. Testosterone treatment was associated with a low-grade inflammatory profile, evidenced by upregulation of proinflammatory plasma proteome (e.g., EN-RAGE, OSM, TNF), and induction of an inflammatory transcriptional program associated with NFkB signaling, and TNF signaling. Following testosterone treatment, higher NFkB activity was revealed in CD4 T, CD8 T, and NK cells in scATACseq analyses. Further, testosterone increased monocytic inflammatory responses upon bacterial stimulation in vitro. Although testosterone was associated with this inflammatory profile, it also exerted negative effects on antiviral immunity. Firstly, the percentage of plasmacytoid dendritic cells (pDC) decreased over transition, with pDC also displaying phenotypic changes associated with lower IFN responses. Secondly, bulk transcriptomics analyses show an overall reduction of IFNa responses. Thirdly, testosterone treatment led to reduced IFNa production upon PBMCs stimulation with a viral agonist. Our results show that testosterone has broad effects on the human immune system, and significantly modulates important players in antiviral immunity and inflammatory response. Identifying pathways involved in immune sexual dimorphism will help define novel targets for effective prevention and treatment of immune-mediated diseases.
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