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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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| 10. |
- 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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- Miniotas, A, et al.
(författare)
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Misfit strain induced lattice distortions in heteroepitaxially grown LaxCa1-xMnO3 thin films studied by extended x-ray absorption fine structure and high-resolution x-ray diffraction
- 2001
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 89:4, s. 2134-2137
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Tidskriftsartikel (refereegranskat)abstract
- Mn-O and Mn-Mn interatomic distances were determined in LaxCa1-xMnO3 films grown heteroepitaxially on single crystal SrTiO3 and LaAlO3 substrates by molecular beam epitaxy. Mn-O bond lengths were found to be fixed at similar to1.975 Angstrom for both types of substrates, while the Mn-Mn distance was detected to be larger for films grown on SrTiO3 substrates than for films grown on LaAlO3. The deviation of Mn-Mn interatomic distances, and subsequently Mn-O-Mn bond angles, in epitaxial LaxCa1-xMnO3 films is attributed to the misfit strain: compressive for LaAlO3 and tensile for SrTiO3 substrates. (C) 2001 American Institute of Physics.
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- Rhoades, Nicholas A., et al.
(författare)
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Identification of rfk-1, a Meiotic Driver Undergoing RNA Editing in Neurospora
- 2019
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Ingår i: Genetics. - : GENETICS SOCIETY AMERICA. - 0016-6731 .- 1943-2631. ; 212:1, s. 93-110
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Tidskriftsartikel (refereegranskat)abstract
- Sk-2 is a meiotic drive element that was discovered in wild populations of Neurospora fungi over 40 years ago. While early studies quickly determined that Sk-2 transmits itself through sexual reproduction in a biased manner via spore killing, the genetic factors responsible for this phenomenon have remained mostly unknown. Here, we identify and characterize rfk-1, a gene required for Sk-2-based spore killing. The rfk-1 gene contains four exons, three introns, and two stop codons, the first of which undergoes RNA editing to a tryptophan codon during sexual development. Translation of an unedited rfk-1 transcript in vegetative tissue is expected to produce a 102-amino acid protein, whereas translation of an edited rfk-1 transcript in sexual tissue is expected to produce a protein with 130 amino acids. These findings indicate that unedited and edited rfk-1 transcripts exist and that these transcripts could have different roles with respect to the mechanism of meiotic drive by spore killing. Regardless of RNA editing, spore killing only succeeds if rfk-1 transcripts avoid silencing caused by a genome defense process called meiotic silencing by unpaired DNA (MSUD). We show that rfk-1's MSUD avoidance mechanism is linked to the genomic landscape surrounding the rfk-1 gene, which is located near the Sk-2 border on the right arm of chromosome III. In addition to demonstrating that the location of rfk-1 is critical to spore-killing success, our results add to accumulating evidence that MSUD helps protect Neurospora genomes from complex meiotic drive elements.
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| 26. |
- Ropponen, A, et al.
(författare)
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Health-related risk factors for disability pensions due to musculoskeletal diagnoses: a 30-year Finnish twin cohort study
- 2011
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Ingår i: Scandinavian journal of public health. - : SAGE Publications. - 1651-1905 .- 1403-4948. ; 39:8, s. 839-848
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Tidskriftsartikel (refereegranskat)abstract
- Aims: There is a need to better understand work incapacity due to musculoskeletal disorders (MSD) and the factors that contribute to being granted disability pension (DP) with such disorders. A twin cohort study would serve a powerful tool responding to this knowledge gap by providing information on factors affecting DP when controlling for family background. The purpose was to investigate the incidence of and risk factors for DP due to any MSD ( n = 1,819) and specifically due to osteoarthritis (OA, n = 677) in a twin cohort of 24,043 people over a 30-year follow-up. Methods: Data on twin pairs from a mailed questionnaire during the baseline year of 1975 were followed up with register data regarding DP, emigration, old-age pension, and death. For statistical analysis, univariate and multivariate Cox proportional hazard ratios were estimated. Results: Baseline musculoskeletal pain, frequency of use of analgesics, body mass index, and chronic diseases, as well as education and social class were significant risk factors for DP due to MSD at follow-up in both sexes. These factors were also the significant predictors of DP due to OA in men. In women, DP due to OA was best predicted by baseline musculoskeletal pain and lower social class. Conclusions: The risk of DP due to MSD and OA seemed to be influenced by comorbidities, educational level and social class. Analyses of twin pairs discordant for DP confirmed the results. Accumulated health problems and chronic conditions during the life course may lead to permanent work incapacity.
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| 27. |
- Ropponen, A, et al.
(författare)
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Night Work and Sustainable Working Life-A Prospective Trajectory Analysis of Swedish Twins
- 2022
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Ingår i: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 19:17
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to investigate the changes in sustainable working life over 10–13 years of follow-up and the effect of baseline night work. Data from the Swedish national registers were used to define sustainable working life. Survey data in the 1998–2003 “SALT” with 34,680 twins or in the 2004–2006 “STAGE” with 19,637 twins were utilized to assess night work at baseline. Group-based trajectory and multinomial regression models were applied. The results of the SALT cohort yielded five trajectory solutions: stable sustainable working life (40%), stable lack of sustainable working life (25%), later decreasingly sustainable working life (15%), increasingly sustainable working life (14%), and early decreasingly sustainable working life (7%). In the STAGE cohort, four trajectories were detected: stable sustainable working life (83%), decreasingly sustainable working life (7%), stable lack of sustainable working life (5%), and increasing sustainable working life (5%). Night work was associated with the decreasing or increasing sustainable working life in the trajectory groups. To conclude, the largest parts of both cohorts followed trajectories of stable sustainable working lives. Night work was associated with both the trajectories of decreasing and increasing sustainable working lives.
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| 31. |
- Skoglund, Karin, et al.
(författare)
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In vivo CYP3A activity and pharmacokinetics of imatinib in relation to therapeutic outcome in chronic myeloid leukemia patients
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: The hepatic enzymes CYP3A4 and CYP3A5 metabolize the tyrosine kinase inhibitor imatinib into a large number of metabolites including the pharmacologically active N-desmethyl imatinib (CGP74588). Because the metabolic activity of CYP3A varies considerably between individuals and a previous pilot study suggested an inverse association between in vivo CYP3A metabolic activity and therapeutic outcome of imatinib, the primary aim of this study was to investigate the influence of CYP3A metabolic activity on the outcome of imatinib therapy in chronic myeloid leukemia patients.Methods: Fifty-five patients were included and CYP3A activity was estimated in vivo using quinine as a probe drug. Imatinib and CGP74588 trough concentrations in the plasma were determined at steady state in 34 patients. Cytogenetic and molecular responses after 12 months of first-line imatinib were retrospectively collected from patients’ medical records.Results: Patients with optimal response to imatinib (complete cytogenetic response (CCgR) or molecular response of BCR-ABL <1%) did not have different levels of CYP3A activity compared to non-optimal responders. Similar results were found when analyzing the molecular response and CCgR separately. Neither the imatinib trough concentration nor the CGP74588/imatinib ratio were significantly associated with CYP3A activity.Conclusion: CYP3A enzyme activity, as measured by quinine metabolic ratio, does not correlate with the plasma concentrations of imatinib or CGP74588 and is not predictive of imatinib therapeutic outcome. These results indicate that even though imatinib is metabolized by CYP3A enzymes, this activity is not the ratelimiting step in imatinib metabolism and excretion. Future studies should focus on other pharmacokinetic processes such as plasma protein binding or transport protein activity to look for the major contributor to patient variability in imatinib plasma concentration.
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| 32. |
- Svedberg, Jesper, et al.
(författare)
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An introgressed gene causes meiotic drive in Neurospora sitophila
- 2021
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 118:17
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Tidskriftsartikel (refereegranskat)abstract
- Meiotic drive elements cause their own preferential transmission following meiosis. In fungi, this phenomenon takes the shape of spore killing, and in the filamentous ascomycete Neurospora sitophila, the Sk-1 spore killer element is found in many natural populations. In this study, we identify the gene responsible for spore killing in Sk-1 by generating both long- and short-read genomic data and by using these data to perform a genome-wide association test. We name this gene Spk-1. Through molecular dissection, we show that a single 405-nt-long open reading frame generates a product that both acts as a poison capable of killing sibling spores and as an antidote that rescues spores that produce it. By phylogenetic analysis, we demonstrate that the gene has likely been introgressed from the closely related species Neurospora hispaniola, and we identify three subclades of N. sitophila, one where Sk-1 is fixed, another where Sk-1 is absent, and a third where both killer and sensitive strain are found. Finally, we show that spore killing can be suppressed through an RNA interference-based genome defense pathway known as meiotic silencing by unpaired DNA. Spk-1 is not related to other known meiotic drive genes, and similar sequences are only found within Neurospora. These results shed light on the diversity of genes capable of causing meiotic drive, their origin and evolution, and their interaction with the host genome.
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| 40. |
- Castro, Daniele Oliveira, et al.
(författare)
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The use of a pilot-scale continuous paper process for fire retardant cellulose-kaolinite nanocomposites
- 2018
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Ingår i: Composites Science And Technology. - : Elsevier Ltd. - 0266-3538 .- 1879-1050. ; 162, s. 215-224
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Tidskriftsartikel (refereegranskat)abstract
- Nanostructured materials are difficult to prepare rapidly and at large scale. Melt-processed polymer-clay nanocomposites are an exception, but the clay content is typically below 5 wt%. An approach for manufacturing of microfibrillated cellulose (MFC)/kaolinite nanocomposites is here demonstrated in pilot-scale by continuous production of hybrid nanopaper structures with thickness of around 100 μm. The colloidal nature of MFC suspensions disintegrated from chemical wood fiber pulp offers the possibility to add kaolinite clay platelet particles of nanoscale thickness. For initial lab scale optimization purposes, nanocomposite processing (dewatering, small particle retention etc) and characterization (mechanical properties, density etc) were investigated using a sheet former (Rapid Köthen). This was followed by a continuous fabrication of composite paper structures using a pilot-scale web former. Nanocomposite morphology was assessed by scanning electron microscopy (SEM). Mechanical properties were measured in uniaxial tension. The fire retardancy was evaluated by cone calorimetry. Inorganic hybrid composites with high content of in-plane oriented nanocellulose, nanoclay and wood fibers were successfully produced at pilot scale. Potential applications include fire retardant paperboard for semi structural applications and as reinforcement mats in molded thermoset biocomposites.
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| 43. |
- Dorner, Thomas E., et al.
(författare)
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Course and characteristics of work disability 3 years before and after lumbar spine decompression surgery : a national population-based study
- 2018
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Despite decompression surgery being a widespread intervention for patients with dorsopathies (i.e. back pain) affecting the lumbar spine, the scientific knowledge on patterns and characteristics of work disability before and after the surgery is limited. Sickness absence (SA) and disability pension (DP) were examined three years before and after surgery in 8558 patients aged 25-60 years who underwent lumbar spine decompression surgery in Sweden. They were compared to individuals with diagnosed dorsopathies but no surgery and individuals from the general population as matched comparison groups. According to Group Based Trajectory models, in patients with decompression surgery, 39% had low levels of SA/DP during the entire study period and 15% started with low levels of SA/DP, which increased in the year before, and declined to almost zero in the second year after surgery. Three trajectory groups (12%, 17%, and 18%) started at different levels of SA/DP, which increased in the years before, and declined in the third year after surgery. The trajectory groups in the comparison groups showed lower levels of work disability. Sex, education, and the use of antidepressants and analgesics the year before surgery played an important role to explain the variance of trajectory groups in patients with surgery.
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| 44. |
- Dorner, Thomas E., et al.
(författare)
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Diagnosis-Specific Work Disability before and after Lumbar Spine Decompression Surgery-A Register Study from Sweden
- 2021
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 18:17
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Tidskriftsartikel (refereegranskat)abstract
- Low back pain (LBP) patients undergoing lumbar spine decompression surgery (LSDS) often suffer from multi-comorbidity and experience high work disability. This study aimed to identify diagnosis-specific work disability patterns in all LBP-patients before and after LSDS during 2008-2010, that were aged 19-60 years and living in Sweden (n = 10,800) and compare these patterns to LBP-patients without LSDS (n = 109,179), and to matched individuals without LBP (n = 472,191). Work disability days (long-term sickness absence (LTSA), disability pension (DP)) during the three years before to three years after the cohort's entry date were identified by generalised estimating equations. LBP-patients undergoing LSDS had higher overall work disability during the three years following surgery (LTSA: 23.6%, DP: 6.3%) than LBP-patients without LSDS (LTSA: 19.5%, DP: 5.9%), and those without LBP (LTSA: 7.9%, DP: 1.7%). Among patients undergoing LSDS, the prevalence of work disability due to dorsopathies increased from 20 days three years before surgery to 70 days in the year after and attenuated to 30 days in the third year following surgery. Work disability for other diagnoses remained stable at a low level in this group (<10 days annually). LBP-patients undergoing LSDS have an unfavourable long-term work disability prognosis, primarily due to dorsopathies. Decompression surgery seemed to restrict further inclines in work disability in the long run.
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| 45. |
- Dorner, T E, et al.
(författare)
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Synergistic effect between back pain and common mental disorders and the risk of future disability pension : a nationwide study from Sweden.
- 2016
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Ingår i: Psychological Medicine. - 0033-2917 .- 1469-8978. ; 46:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of this study was to analyse a possible synergistic effect between back pain and common mental disorders (CMDs) in relation to future disability pension (DP).METHOD: All 4 823 069 individuals aged 16-64 years, living in Sweden in December 2004, not pensioned in 2005 and without ongoing sickness absence at the turn of 2004/2005 formed the cohort of this register-based study. Hazard ratios (HRs) and 95% confidence intervals (CIs) for DP (2006-2010) were estimated. Exposure variables were back pain (M54) (sickness absence or inpatient or specialized outpatient care in 2005) and CMD (F40-F48) [sickness absence or inpatient or specialized outpatient care or antidepressants (N06a) in 2005].RESULTS: HRs for DP were 4.03 (95% CI 3.87-4.21) and 3.86 (95% CI 3.68-4.04) in women and men with back pain. HRs for DP in women and men with CMD were 4.98 (95% CI 4.88-5.08) and 6.05 (95% CI 5.90-6.21). In women and men with both conditions, HRs for DP were 15.62 (95% CI 14.40-16.94) and 19.84 (95% CI 17.94-21.94). In women, synergy index, relative excess risk due to interaction, and attributable proportion were 1.24 (95% CI 1.13-1.36), 0.18 (95% CI 0.11-0.25), and 2.08 (95% CI 1.09-3.06). The corresponding figures for men were 1.45 (95% CI 1.29-1.62), 0.29 (95% CI 0.22-0.36), and 4.21 (95% CI 2.71-5.70).CONCLUSIONS: Co-morbidity of back pain and CMD is associated with a higher risk of DP than either individual condition, when added up, which has possible clinical implications to prevent further disability and exclusion from the labour market.
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| 47. |
- Ernstgard, L, et al.
(författare)
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Acute effects of exposure to hexanal vapors in humans
- 2006
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Ingår i: Journal of occupational and environmental medicine. - : Ovid Technologies (Wolters Kluwer Health). - 1076-2752. ; 48:6, s. 573-580
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Tidskriftsartikel (refereegranskat)
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