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- Sellgren, C. M., et al.
(författare)
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GRK3 deficiency elicits brain immune activation and psychosis
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26, s. 6820-6832
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Tidskriftsartikel (refereegranskat)abstract
- The G protein-coupled receptor kinase (GRK) family member protein GRK3 has been linked to the pathophysiology of schizophrenia and bipolar disorder. Expression, as well as protein levels, of GRK3 are reduced in post-mortem prefrontal cortex of schizophrenia subjects. Here, we investigate functional behavior and neurotransmission related to immune activation and psychosis using mice lacking functional Grk3 and utilizing a variety of methods, including behavioral, biochemical, electrophysiological, molecular, and imaging methods. Compared to wildtype controls, the Grk3(-/-) mice show a number of aberrations linked to psychosis, including elevated brain levels of IL-1 beta, increased turnover of kynurenic acid (KYNA), hyper-responsiveness to D-amphetamine, elevated spontaneous firing of midbrain dopamine neurons, and disruption in prepulse inhibition. Analyzing human genetic data, we observe a link between psychotic features in bipolar disorder, decreased GRK expression, and increased concentration of CSF KYNA. Taken together, our data suggest that Grk3(-/-) mice show face and construct validity relating to the psychosis phenotype with glial activation and would be suitable for translational studies of novel immunomodulatory agents in psychotic disorders.
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- Björkenheim, Anna, 1980-, et al.
(författare)
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Does zero atrial fibrillation burden after atrial fibrillation ablation mean that patients are free of symptoms?
- 2017
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Ingår i: Europace, Supplements. - : Oxford University Press. - 1099-6044 .- 1749-365X. ; 19:Duppl. 3, s. iii264-iii264
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Success of atrial fibrillation (AF) ablation is usually defined as freedom of AF, although symptomatic relief often is what the patient’s desire. After ablation the proportion of ‘silent’ AF increases and success based on symptomatic AF recurrence may be overestimated.Purpose: To investigate the symptomatology of patients who are truly free of AF after ablation.Methods: In 57 patients the symptomatology after AF ablation was assessed as perceived by the patient using a validated AF-specific symptom questionnaire (AF6) and the overall treatment effect (OTE), and as classified by the physician using the EHRA score, at baseline, 6, 12 and 24 months. The cardiac rhythm was continuously monitored by an implantable loop recorder throughout the 2-year follow-up.Results: At 6, 12 and 24 months 14 (26%), 23 (43%) and 23 (43%) patients had an AF burden 0% during the past 6 months, and 13 of them had an AF burden 0% during the entire 2 year follow-up. All patients reported ‘OTE better’ at all time-points. All patients were also classified into EHRA I at 6 months. Being completely free of AF for six months periods did not mean complete freedom of symptoms, but the median AF6 sum score was consistently low with a narrowing IQR over time, 0 (IQR 0-27), 0.5 (IQR 0-7) and 0 (IQR 0-11) at 6, 12 and 24 months. At 6 months 8/14 patients (57%) scored AF6=0, the others 6, 11, 26, 28, 30 and 46 points. At 12 months 13/23 patients (56%) scored AF6=0, the others 1,1,3,3,5,7,7,7,14 and 22 points. At 24 months 12/23 (52%) patients scored AF6=0, the others 1, 1, 2, 4, 9, 11, 17, 20, 24, 32 and 42 points. Among the AF6 items, ‘worry/anxiety due to AF’ was the most common, while ‘tiredness due to AF’ was the highest scoring item. In the patients with AF burden 0% during the entire 2-year follow-up all patients were improved in OTE and all patients were classified into EHRA class I at all times after ablation and the median AF6 sum score was 4 (IQR0-28), 0.5 (IQR 0-8) and 1 (0-5) at 6, 12 and 24 months after ablation.Conclusions: Sudden elimination of AF by ablation does not automatically eliminate all symptoms that the patients associated with AF, but all patients felt better and were classified in EHRA class I at all time-points. Less than a half of the patients at any time-point scored some symptoms, but the symptoms gradually decreased over time, especially between 6 and 12 months.
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- Ahlinder, J., et al.
(författare)
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Use of metagenomic microbial source tracking to investigate the source of a foodborne outbreak of cryptosporidiosis
- 2022
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Ingår i: FOOD AND WATERBORNE PARASITOLOGY. - : Elsevier. - 2405-6766. ; 26
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Tidskriftsartikel (refereegranskat)abstract
- Cryptosporidium is a protozoan parasite of global public health importance that causes gastroenteritis in a variety of vertebrate hosts, with many human outbreaks reported yearly, often from ingestion of contaminated water or food. Despite the major public health implications, little is typically known about sources of contamination of disease outbreaks caused by Cryptosporidium. Here, we study a national foodborne outbreak resulted from infection with Cryptosporidium parvum via romaine lettuce, with the main goal to trace the source of the parasite. To do so, we combined traditional outbreak investigation methods with molecular detection and characterization methods (i.e. PCR based typing, amplicon and shotgun sequencing) of romaine lettuce samples collected at the same farm from which the contaminated food was produced. Using 18S rRNA typing, we detected C. parvum in two out of three lettuce samples, which was supported by detections in the metagenome analysis. Microbial source tracking analysis of the lettuce samples suggested sewage water as a likely source of the contamination, albeit with some uncertainty. In addition, the high degree of overlap in bacterial species content with a public human gut microbial database corroborated the source tracking results. The combination of traditional and molecular based methods applied here is a promising tool for future source tracking investigations of food- and waterborne outbreaks of Cryptosporidium spp. and can help to control and mitigate contamination risks.
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- Domeij, Martin, et al.
(författare)
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2.2 kV SiC BJTs with low V(CESAT) fast switching and short-circuit capability
- 2010
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Ingår i: SILICON CARBIDE AND RELATED MATERIALS 2009, PTS 1 AND 2. ; , s. 1033-1036
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Konferensbidrag (refereegranskat)abstract
- This paper reports large active area (15 mm(2)) 4H-SiC BJTS with a low V(CESAT)=0.6 V at 1(C)=20 A (J(C)=133 A/cm(2)) and an open-base breakdown voltage BV(CEO)=2.3 kV at T=25 degrees C. The corresponding room temperature specific on-resistance R(SP.ON)=4.5 m Omega cm(2) is to the authors knowledge the lowest reported value for a large area SiC BJT blocking more than 2 kV. The onstate and blocking characteristics were analyzed by device simulation and found to be in good agreement with measurements. Fast switching with VcE rise- and fall-times in the range of 20-30 ns was demonstrated for a 6 A 1200 V rated SiC BJT. It was concluded that high dynamic base currents are essential for fast switching to charge the BJT parasitic base-collector capacitance. In addition, 10 mu s short-circuit capability with V(CE)=800 V was shown for the 1200 V BJT.
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