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- Muus, Christoph, et al.
(författare)
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Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics
- 2021
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:3, s. 546-559
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Tidskriftsartikel (refereegranskat)abstract
- Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2(+)TMPRSS2(+) cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention. An integrated analysis of over 100 single-cell and single-nucleus transcriptomics studies illustrates severe acute respiratory syndrome coronavirus 2 viral entry gene coexpression patterns across different human tissues, and shows association of age, smoking status and sex with viral entry gene expression in respiratory cell populations.
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- Legendre, C. M., et al.
(författare)
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Terminal Complement Inhibitor Eculizumab in Atypical Hemolytic-Uremic Syndrome
- 2013
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 368:23, s. 2169-2181
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Tidskriftsartikel (refereegranskat)abstract
- Background Atypical hemolytic-uremic syndrome is a genetic, life-threatening, chronic disease of complement-mediated thrombotic microangiopathy. Plasma exchange or infusion may transiently maintain normal levels of hematologic measures but does not treat the underlying systemic disease. Methods We conducted two prospective phase 2 trials in which patients with atypical hemolytic-uremic syndrome who were 12 years of age or older received eculizumab for 26 weeks and during long-term extension phases. Patients with low platelet counts and renal damage (in trial 1) and those with renal damage but no decrease in the platelet count of more than 25% for at least 8 weeks during plasma exchange or infusion (in trial 2) were recruited. The primary end points included a change in the platelet count (in trial 1) and thrombotic microangiopathy event-free status (no decrease in the platelet count of >25%, no plasma exchange or infusion, and no initiation of dialysis) (in trial 2). Results A total of 37 patients (17 in trial 1 and 20 in trial 2) received eculizumab for a median of 64 and 62 weeks, respectively. Eculizumab resulted in increases in the platelet count; in trial 1, the mean increase in the count from baseline to week 26 was 73x10(9) per liter (P<0.001). In trial 2, 80% of the patients had thrombotic microangiopathy event-free status. Eculizumab was associated with significant improvement in all secondary end points, with continuous, time-dependent increases in the estimated glomerular filtration rate (GFR). In trial 1, dialysis was discontinued in 4 of 5 patients. Earlier intervention with eculizumab was associated with significantly greater improvement in the estimated GFR. Eculizumab was also associated with improvement in health-related quality of life. No cumulative toxicity of therapy or serious infection-related adverse events, including meningococcal infections, were observed through the extension period. Conclusions Eculizumab inhibited complement-mediated thrombotic microangiopathy and was associated with significant time-dependent improvement in renal function in patients with atypical hemolytic-uremic syndrome.
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- Saarento, O, et al.
(författare)
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The Nordic Comparative Study on Sectorized Psychiatry : continuity of care related to characteristics of the psychiatric services and the patients.
- 1998
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Ingår i: Social Psychiatry and Psychiatric Epidemiology. - 0933-7954 .- 1433-9285. ; 33:11, s. 521-7
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Tidskriftsartikel (refereegranskat)abstract
- The problem addressed in this paper is how continuity of care is related to characteristics of psychiatric services, previous events in a patient's pattern of care and patient characteristics. The present paper is a part of a Nordic Comparative Study on Sectorized Psychiatry in seven catchment areas in four Nordic countries. One-year-treated-incidence cohorts were used. Each patient was followed for 1 year after the first contact with the psychiatric service. Continuity of care was measured by the time from discharge from hospital to the first subsequent day-patient or outpatient contact. Notable findings were large differences in the continuity of care in the seven services, high proportions of discharges without any aftercare contacts and long time lags between discharges and aftercare contacts in most of the catchment areas. A Cox regression analysis revealed that aftercare following hospitalisation seems to be more probable if the outpatient services are located geographically close to the patients, if the hospitalisation lasted between 2 and 4 weeks, if there was a community care contact shortly before the hospital admission and if the patient is not retired and not divorced. Staff resources were not related to continuity of care.
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| 8. |
- Hansson, L, et al.
(författare)
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The Nordic Comparative Study on Sectorized Psychiatry : contact rates and use of services for patients with a functional psychosis.
- 1998
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Ingår i: Acta Psychiatrica Scandinavica. - 0001-690X .- 1600-0447. ; 97:5, s. 315-20
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Tidskriftsartikel (refereegranskat)abstract
- As part of a Nordic comparative study on contact rates of new patients and use of services in seven catchment areas, contact rates and use of services for patients with a functional psychosis during a 1-year follow-up period were investigated. The highest contact rates were found in two large city catchment areas in Stockholm and Copenhagen. Compared to other patients in the cohorts, patients with a functional psychosis were more often found to be unemployed and living alone. They also showed more extensive service use in terms of both voluntary and compulsory admissions, and in the use of day-care facilities. In addition, they were more often multiple users of in-patient care (> or =3 admissions during the follow-up period). Large differences in service use among patients with a functional psychosis were discovered between the catchment areas, with the most extensive use of voluntary in-patient care and day-care facilities in Frederiksberg. Patients most frequently had compulsory admissions in Bodö and least frequently had them in Frederiksberg. Out-patient services were most frequently used in Stockholm. Correlations between levels of resources and use of services for patients with a functional psychosis were in general low, except for the rates of short-term beds, which showed a strong and significant correlation with the number of days in voluntary in-patient care (r=0.89).
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