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- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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- Bellenguez, C, et al.
(författare)
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New insights into the genetic etiology of Alzheimer's disease and related dementias
- 2022
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
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Tidskriftsartikel (refereegranskat)abstract
- Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
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- Bousquet, J, et al.
(författare)
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Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies
- 2020
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Ingår i: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 10:1, s. 58-
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Tidskriftsartikel (refereegranskat)abstract
- There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.
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- Garcia-Garcia, A, et al.
(författare)
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Humans with inherited MyD88 and IRAK-4 deficiencies are predisposed to hypoxemic COVID-19 pneumonia
- 2023
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 220:5
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Tidskriftsartikel (refereegranskat)abstract
- X-linked recessive deficiency of TLR7, a MyD88- and IRAK-4–dependent endosomal ssRNA sensor, impairs SARS-CoV-2 recognition and type I IFN production in plasmacytoid dendritic cells (pDCs), thereby underlying hypoxemic COVID-19 pneumonia with high penetrance. We report 22 unvaccinated patients with autosomal recessive MyD88 or IRAK-4 deficiency infected with SARS-CoV-2 (mean age: 10.9 yr; 2 mo to 24 yr), originating from 17 kindreds from eight countries on three continents. 16 patients were hospitalized: six with moderate, four with severe, and six with critical pneumonia, one of whom died. The risk of hypoxemic pneumonia increased with age. The risk of invasive mechanical ventilation was also much greater than in age-matched controls from the general population (OR: 74.7, 95% CI: 26.8–207.8, P < 0.001). The patients’ susceptibility to SARS-CoV-2 can be attributed to impaired TLR7-dependent type I IFN production by pDCs, which do not sense SARS-CoV-2 correctly. Patients with inherited MyD88 or IRAK-4 deficiency were long thought to be selectively vulnerable to pyogenic bacteria, but also have a high risk of hypoxemic COVID-19 pneumonia.
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- Klimek, L, et al.
(författare)
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Anwendung von Biologika bei allergischen und Typ-2-entzündlichen Erkrankungen in der aktuellen Covid-19-Pandemiea, b, c: Positionspapier des Ärzteverbands Deutscher Allergologen (AeDA)A, der Deutschen Gesellschaft für Allergologie und klinische Immunologie (DGAKI)B, der Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA)C, der Österreichischen Gesellschaft für Allergologie und Immunologie (ÖGAI)D, der Luxemburgischen Gesellschaft für Allergologie und Immunologie (LGAI)E, der Österreichischen Gesellschaft für Pneumologie (ÖGP)F in Kooperation mit der deutschen, österreichischen, und schweizerischen ARIA-GruppeG und der Europäischen Akademie für Allergologie und Klinische Immunologie (EAACI)H
- 2020
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Ingår i: Allergo Journal : interdisziplinare Zeitschrift fur Allergologie und Umweltmedizin : Organ der Deutschen Gesellschaft fur Allergie- und Immunitatsforschung. - : Springer Science and Business Media LLC. - 0941-8849. ; 29:4, s. 14-27
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Tidskriftsartikel (refereegranskat)
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25. |
- Klimek, L, et al.
(författare)
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Use of biologicals in allergic and type-2 inflammatory diseases during the current COVID-19 pandemic: Position paper of Ärzteverband Deutscher Allergologen (AeDA)A, Deutsche Gesellschaft für Allergologie und Klinische Immunologie (DGAKI)B, Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA)C, Österreichische Gesellschaft für Allergologie und Immunologie (ÖGAI)D, Luxemburgische Gesellschaft für Allergologie und Immunologie (LGAI)E, Österreichische Gesellschaft für Pneumologie (ÖGP)F in co-operation with the German, Austrian, and Swiss ARIA groupsG, and the European Academy of Allergy and Clinical Immunology (EAACI)H
- 2020
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Ingår i: Allergologie select. - 2512-8957. ; 4, s. 53-68
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Tidskriftsartikel (refereegranskat)
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