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- Assaf, Sara, et al.
(författare)
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Asthma in the era of COVID-19
- 2023
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Ingår i: Respiratory Medicine. - 0954-6111. ; 218
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Tidskriftsartikel (refereegranskat)abstract
- Since its global invasion in 2019, COVID-19 has affected several aspects of patients’ lives and posed a significant impact on the health care system. Several patient populations were identified to be at high risk of contracting SARS-CoV-2 infection and/or developing severe COVID-19-related sequelae. Conversely, anyone who has contracted SARS-CoV-2 is at risk to experience symptoms and signs consistent with post-COVID manifestations. Patients with asthma were initially thought to be at increased risk and severity for SARS-CoV-2 infection. However, accumulating evidence demonstrates that asthma endotypes/phenotypes and comorbidities influence the risk stratification in this population. Furthermore, initial concerns about the potentially increased risk of poor outcomes with asthma treatments such as inhaled corticosteroids and biologics have not been substantiated. In this review, we provide an update on COVID-19 and asthma, including risk of susceptibility, clinical manifestations and course in this population as well as discuss recommendations for management.
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- Assaf, Sara M., et al.
(författare)
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Asthma and severe acute respiratory syndrome coronavirus 2019 : current evidence and knowledge gaps
- 2021
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Ingår i: Current Opinion in Pulmonary Medicine. - 1531-6971. ; 27:1, s. 45-53
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE OF REVIEW: Although respiratory viruses are common triggers of asthma exacerbation, it is unknown whether this also applies to infection with SARS-CoV-2. Indeed, patients with asthma and allergy appear underrepresented in large reports of COVID-19 cases worldwide. In this review, we evaluate existing literature on this topic and potential underlying mechanisms for any interrelationship between asthma and COVID-19. RECENT FINDINGS: Data from several preclinical and clinical reports suggest a lower susceptibility for COVID-19 in patients with underlying type 2 airway inflammation including asthma that may be related to a reduced expression of ACE2 and TMPRSS2 receptors for SARS-CoV-2. Corticosteroids further decrease expression of the ACE2 and TMPRSS2 receptors, hence may also have a protective effect against infection with SARS-CoV-2. In addition, some studies suggest that the reported improvement in asthma control and a reduction in asthma exacerbations during the COVID-19 pandemic may be related to improvement in adherence to controller therapy and reduced exposure to triggers, such as other respiratory viruses and air pollutants. Recent data point towards differential susceptibility for COVID-19 among asthma patients based on their phenotype and/or endotype. On the basis of existing evidence, continuation with controller therapies is recommended for all patients with asthma. For patients with severe uncontrolled asthma infected by SARS-CoV-2, adjustment of controllers and biologics should be based on a multidisciplinary decision. SUMMARY: Underrepresentation of SARS-CoV-2-infected patients with asthma and related allergic diseases may be based on potentially protective underlying mechanisms, such as type 2 airway inflammation, downregulation of ACE2/TMPRSS2 receptors, reduced exposures to triggers and improved adherence to controller medications. Although it is imperative that control should be maintained and asthma medications be continued in all patients, management of patients with severe uncontrolled asthma infected by SARS-CoV-2 including adjustment of controllers and biologics should be discussed on an individual basis.
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- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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- Mercer, Laina D., et al.
(författare)
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Comparing universal kriging and land-use regression for predicting concentrations of gaseous oxides of nitrogen (NOx) for the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air)
- 2011
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Ingår i: Atmospheric Environment. - : Elsevier BV. - 1352-2310. ; 45:26, s. 4412-4420
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epidemiological studies that assess the health effects of long-term exposure to ambient air pollution are used to inform public policy. These studies rely on exposure models that use data collected from pollution monitoring sites to predict exposures at subject locations. Land-use regression (LUR) and universal kriging (UK) have been suggested as potential prediction methods. We evaluate these approaches on a dataset including measurements from three seasons in Los Angeles, CA. Methods: The measurements of gaseous oxides of nitrogen (NOx) used in this study are from a "snapshot" sampling campaign that is part of the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air). The measurements in Los Angeles were collected during three two-week periods in the summer, autumn, and winter, each with about 150 sites. The design included clusters of monitors on either side of busy roads to capture near-field gradients of traffic-related pollution. LUR and UK prediction models were created using geographic information system (GIS)-based covariates. Selection of covariates was based on 10-fold cross-validated (CV) R-2 and root mean square error (RMSE). Since UK requires specialized software, a computationally simpler two-step procedure was also employed to approximate fitting the UK model using readily available regression and GIS software. Results: UK models consistently performed as well as or better than the analogous LUR models. The best CV R-2 values for season-specific UK models predicting log(NOx) were 0.75, 0.72, and 0.74 (CV RMSE 0.20, 0.17, and 0.15) for summer, autumn, and winter, respectively. The best CV R-2 values for season-specific LUR models predicting log(NOx) were 0.74, 0.60, and 0.67 (CV RMSE 0.20, 0.20, and 0.17). The two-stage approximation to UK also performed better than LUR and nearly as well as the full UK model with CV R-2 values 0.75, 0.70, and 0.70 (CV RMSE 0.20, 0.17, and 0.17) for summer, autumn, and winter, respectively. Conclusion: High quality LUR and UK prediction models for NOx in Los Angeles were developed for the three seasons based on data collected for MESA Air. In our study, UK consistently outperformed LUR. Similarly, the 2-step approach was more effective than the LUR models, with performance equal to or slightly worse than UK. (C) 2011 Elsevier Ltd. All rights reserved.
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| 7. |
- Stein, Robert, et al.
(författare)
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A tidal disruption event coincident with a high-energy neutrino
- 2021
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Ingår i: Nature Astronomy. - : Springer Science and Business Media LLC. - 2397-3366. ; :5, s. 510-518
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Tidskriftsartikel (refereegranskat)abstract
- Cosmic neutrinos provide a unique window into the otherwise hidden mechanism of particle acceleration in astrophysical objects. The IceCube Collaboration recently reported the likely association of one high-energy neutrino with a flare from the relativistic jet of an active galaxy pointed towards the Earth. However a combined analysis of many similar active galaxies revealed no excess from the broader population, leaving the vast majority of the cosmic neutrino flux unexplained. Here we present the likely association of a radio-emitting tidal disruption event, AT2019dsg, with a second high-energy neutrino. AT2019dsg was identified as part of our systematic search for optical counterparts to high-energy neutrinos with the Zwicky Transient Facility. The probability of finding any coincident radio-emitting tidal disruption event by chance is 0.5%, while the probability of finding one as bright in bolometric energy flux as AT2019dsg is 0.2%. Our electromagnetic observations can be explained through a multizone model, with radio analysis revealing a central engine, embedded in a UV photosphere, that powers an extended synchrotron-emitting outflow. This provides an ideal site for petaelectronvolt neutrino production. Assuming that the association is genuine, our observations suggest that tidal disruption events with mildly relativistic outflows contribute to the cosmic neutrino flux. The tidal disruption event AT2019dsg is probably associated with a high-energy neutrino, suggesting that such events can contribute to the cosmic neutrino flux. The electromagnetic emission is explained in terms of a central engine, a photosphere and an extended synchrotron-emitting outflow.
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