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- Gilles, Stefanie, et al.
(författare)
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Pollen exposure weakens innate defense against respiratory viruses.
- 2020
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Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 75:3, s. 576-587
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Tidskriftsartikel (refereegranskat)abstract
- Hundreds of plant species release their pollen into the air every year during early spring. During that period, pollen allergic as well as non-allergic patients frequently present to doctors with severe respiratory tract infections.To assess whether pollen may interfere with antiviral immunity.We combined data from real life human exposure cohorts, a mouse model and human cell culture to test our hypothesis.Pollen significantly diminished interferon-λ and pro-inflammatory chemokine responses of airway epithelia to rhinovirus and viral mimics and decreased nuclear translocation of interferon regulatory factors. In mice infected with respiratory syncytial virus, co-exposure to pollen caused attenuated antiviral gene expression and increased pulmonary viral titers. In non-allergic human volunteers, nasal symptoms were positively correlated with airborne birch pollen abundance, and nasal birch pollen challenge led to down-regulation of type I and -III interferons in nasal mucosa. In a large patient cohort, numbers of rhinovirus-positive cases were correlated with airborne birch pollen concentrations.The ability of pollen to suppress innate antiviral immunity, independent of allergy, suggests that high-risk population groups should avoid extensive outdoor activities when pollen and respiratory virus seasons coincide.
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- Hegmar, Hannes, et al.
(författare)
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Liver stiffness predicts progression to liver-related events in patients with chronic liver disease - A cohort study of 14 414 patients
- 2024
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Ingår i: Liver international. - : WILEY. - 1478-3223 .- 1478-3231.
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) is a non-invasive diagnostic biomarker of liver fibrosis. It is uncertain if LSM can predict risk for future liver-related outcomes in large, heterogenous populations. Methods: This Swedish multi-centre cohort study included patients (n = 14 414) from 16 sites who underwent LSM by VCTE between 2008 and 2020. Outcomes were ascertained from national registers. We investigated progression to cirrhosis with portal hypertension or hepatocellular carcinoma (HCC), separately. Cox regression was used to obtain hazard ratios (HRs). Harrel's C-index was used to measure discrimination of VCTE. Results: Included patients had a median age of 46 (interquartile range 34-57), median LSM of 5.9 kPa (4.6-8.0), 59% were male, and the majority had hepatitis C (50.1%). During a median follow-up of 5.9 (4.3-8.0) years, 402 patients (2.7%) developed cirrhosis with portal hypertension. In patients with an LSM >= 25 kPa, 28.7% developed cirrhosis with portal hypertension within 5 years of follow-up, while only .6% of patients with an LSM <10 kPa did. This translated to a HR of 48.3 (95% confidence interval = 37.6-62.0). VCTE had a high discriminative ability, with C-indices above .80 for most liver diseases, including .82 for MASLD. Similar findings were seen for incident HCC. Conclusions: Increased LSM by VCTE was associated with an increased risk of progression to both cirrhosis with portal hypertension, and to HCC, and had a high discriminative ability across different aetiologies of chronic liver diseases. These results support the use of VCTE to guide follow-up and treatment decisions.
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- Lindström, Johan, 1984, et al.
(författare)
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Assessment of the FilmArray ME panel in 4199 consecutively tested cerebrospinal fluid samples
- 2022
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Ingår i: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X. ; 28:1, s. 79-84
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: In central nervous system infections, early and correct management is of utmost importance. Rapid syndromic panel testing can potentially provide valuable guidance. The FilmArray meningitis/encephalitis (ME) panel detects 14 pathogens through multiplex PCR. Our study objectives were to assess its performance compared with established diagnostic procedures, especially real-time quantitative PCR for detection of viruses, and to determine the diagnostic and clinical significance of discrepant results. Methods: All cerebrospinal fluid samples sent for viral diagnostics to our microbiological laboratory over 34 months were analysed with the ME panel and in-house real-time PCR for herpes simplex virus type 1 (HSV-1), HSV-2, varicella zoster virus and enteroviruses. Other pathogens detected by the panel were confirmed by routine diagnostic procedures. Discrepant results were analysed through interpretation of biological and clinical data, and performance data were calculated for individual pathogens. Results: Altogether, 315 pathogens were detected by the ME panel in 4199 cerebrospinal fluid samples (7.5%) and an additional 21 viral targets were identified using real-time PCR. Thirty-four ME panel detections were not confirmed, totalling 55 discrepant results. After discrepancy analysis, 20 false-positive and 21 false-negative ME panel results remained. Performance varied between pathogens. Sensitivity for HSV-1 was calculated at 82.4% (59.0%–93.8%) with three false-negative results. Also noteworthy were 13 false-negative enterovirus and eight false-positive Streptococcus pneumoniae results. Conclusions: Our analysis shows good performance for the ME panel in diagnosing central nervous system infection. The risk of false-negative HSV-1 results, however, warrants additional testing when encephalitis is suspected. Uncertainties in interpretation of enterovirus and S. pneumoniae results represent other limitations. © 2021 The Author(s)
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- Myhrman, Sofia, et al.
(författare)
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Unexpected details regarding nosocomial transmission revealed by whole-genome sequencing of SARS-CoV-2
- 2022
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Ingår i: Infection Control and Hospital Epidemiology. - : Cambridge University Press (CUP). - 0899-823X .- 1559-6834. ; 43:10, s. 1403-1407
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Effective infection prevention and control (IPC) measures are key for protecting patients from nosocomial infections and require knowledge of transmission mechanisms in different settings. We performed a detailed outbreak analysis of the transmission and outcome of coronavirus disease 2019 (COVID-19) in a geriatric ward by combining whole-genome sequencing (WGS) with epidemiological data. Design: Retrospective cohort study. Setting: Tertiary care hospital. Participants: Patients and healthcare workers (HCWs) from the ward with a nasopharyngeal sample (NPS) positive for SARS-CoV-2 RNA during the outbreak period. Methods: Patient data regarding clinical characteristics, exposure and outcome were collected retrospectively from medical records. Stored NPS from 32 patients and 15 HCWs were selected for WGS and phylogenetic analysis. Results: Median patient age was 84 years and 17/32 (53%) were male. Fourteen patients (44%) died within 30 days after sampling. Viral load was significantly higher among the deceased. WGS was successful in 28/32 (88%) patient samples and 14/15 (93%) HCW samples. Three separate viral clades were identified, whereof one clade and two subclades among both patient and HCW samples. Integrated epidemiological and genetic analysis revealed six probable transmission events between patients and supported hospital-acquired COVID-19 in 25/32 patients. Conclusion: WGS provided a deep insight into the outbreak dynamics and true extent of nosocomial COVID-19. The extensive transmission between patients and HCWs indicated that current IPC measures were insufficient. We suggest increased use of WGS in outbreak investigations for identification of otherwise unknown transmission links and evaluation of IPC measures.
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- Thalén, Niklas, 1985-, et al.
(författare)
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Systems biology greatly improve activity of secreted therapeutic sulfatase in CHO bioprocess
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Rare diseases are, despite their name, collectively common and millions of people are affected daily of conditions where treatment often is unavailable. Sulfatases are a large family of activating enzymes related to several of these diseases. Heritable genetic variations in sulfatases may lead to impaired activity and a reduced macromolecular breakdown within the lysosome, with several severe and lethal conditions as a consequence. While therapeutic options are scarce, treatment for some sulfatase deficiencies by recombinant enzyme replacement are available. However, such recombinant production of sulfatases suffers greatly from low product activity and yield, further limiting accessibility for patient groups. Here, we have addressed this problem by defining key-proteins necessary for active sulfatase secretion by comparison of CHO clones with different levels of production of active sulfatase. Quantitative transcriptomic analysis highlighted 14 key genes associated with sulfatase production, and experimental validation by co-expression improved the sulfatase enzyme activity by up to 150-fold. Furthermore, a correlation between product mRNA levels and sulfatase activity were observed and expression with lower activity promoters showed an increased in sulfatase activity. The workflow devised is general and we propose it to be useful for resolving bottlenecks in cellular machineries for improvement of cell factories for other biologics as well.
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