| 1. |
- Bruhn-Olszewska, Bozena, et al.
(författare)
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Loss of Y in leukocytes as a risk factor for critical COVID-19 in men.
- 2022
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Ingår i: Genome medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic, which has a prominent social and economic impact worldwide, shows a largely unexplained male bias for the severity and mortality of the disease. Loss of chromosome Y (LOY) is a risk factor candidate in COVID-19 due to its prior association with many chronic age-related diseases, and its impact on immune gene transcription.Publicly available scRNA-seq data of PBMC samples derived from male patients critically ill with COVID-19 were reanalyzed, and LOY status was added to the annotated cells. We further studied LOY in whole blood for 211 COVID-19 patients treated at intensive care units (ICU) from the first and second waves of the pandemic. Of these, 139 patients were subject to cell sorting for LOY analysis in granulocytes, low-density neutrophils (LDNs), monocytes, and PBMCs.Reanalysis of available scRNA-seq data revealed LDNs and monocytes as the cell types most affected by LOY. Subsequently, DNA analysis indicated that 46%, 32%, and 29% of critically ill patients showed LOY above 5% cut-off in LDNs, granulocytes, and monocytes, respectively. Hence, the myeloid lineage that is crucial for the development of severe COVID-19 phenotype is affected by LOY. Moreover, LOY correlated with increasing WHO score (median difference 1.59%, 95% HDI 0.46% to 2.71%, p=0.025), death during ICU treatment (median difference 1.46%, 95% HDI 0.47% to 2.43%, p=0.0036), and history of vessel disease (median difference 2.16%, 95% HDI 0.74% to 3.7%, p=0.004), among other variables. In 16 recovered patients, sampled during ICU stay and 93-143 days later, LOY decreased significantly in whole blood and PBMCs. Furthermore, the number of LDNs at the recovery stage decreased dramatically (median difference 76.4 per 10,000 cell sorting events, 95% HDI 55.5 to 104, p=6e-11).We present a link between LOY and an acute, life-threatening infectious disease. Furthermore, this study highlights LOY as the most prominent clonal mutation affecting the myeloid cell lineage during emergency myelopoiesis. The correlation between LOY level and COVID-19 severity might suggest that this mutation affects the functions of monocytes and neutrophils, which could have consequences for male innate immunity.
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| 2. |
- Torinsson Naluai, Åsa, 1968, et al.
(författare)
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Transcriptomics unravels molecular changes associated with cilia and COVID-19 in chronic rhinosinusitis with nasal polyps
- 2023
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common upper respiratory tract complication where the pathogenesis is largely unknown. Herein, we investigated the transcriptome profile in nasal mucosa biopsies of CRSwNP patients and healthy individuals. We further integrated the transcriptomics data with genes located in chromosomal regions containing genome-wide significant gene variants for COVID-19. Among the most significantly upregulated genes in polyp mucosa were CCL18, CLEC4G, CCL13 and SLC9A3. Pathways involving "Ciliated epithelial cells" were the most differentially expressed molecular pathways when polyp mucosa and non-polyp mucosa from the same patient was compared. Natural killer T-cell (NKT) and viral pathways were the most statistically significant pathways in the mucosa of CRSwNP patients compared with those of healthy control individuals. Upregulated genes in polyp mucosa, located within the genome-wide associated regions of COVID-19, included LZTFL1, CCR9, SLC6A20, IFNAR1, IFNAR2 and IL10RB. Interestingly, the second most over-expressed gene in our study, CLEC4G, has been shown to bind directly to SARS-CoV-2 spike's N-terminal domain and mediate its entry and infection. Our results on altered expression of genes related to cilia and viruses point to the de-regulation of viral defenses in CRSwNP patients, and may give clues to future intervention strategies.
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| 3. |
- Andersson, Linda, 1973, et al.
(författare)
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Glucosylceramide synthase deficiency in the heart compromises β1-adrenergic receptor trafficking
- 2021
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:43, s. 4481-4492
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Cardiac injury and remodelling are associated with the rearrangement of cardiac lipids. Glycosphingolipids are membrane lipids that are important for cellular structure and function, and cardiac dysfunction is a characteristic of rare monogenic diseases with defects in glycosphingolipid synthesis and turnover. However, it is not known how cardiac glycosphingolipids regulate cellular processes in the heart. The aim of this study is to determine the role of cardiac glycosphingolipids in heart function.METHODS AND RESULTS: Using human myocardial biopsies, we showed that the glycosphingolipids glucosylceramide and lactosylceramide are present at very low levels in non-ischaemic human heart with normal function and are elevated during remodelling. Similar results were observed in mouse models of cardiac remodelling. We also generated mice with cardiomyocyte-specific deficiency in Ugcg, the gene encoding glucosylceramide synthase (hUgcg-/- mice). In 9- to 10-week-old hUgcg-/- mice, contractile capacity in response to dobutamine stress was reduced. Older hUgcg-/- mice developed severe heart failure and left ventricular dilatation even under baseline conditions and died prematurely. Using RNA-seq and cell culture models, we showed defective endolysosomal retrograde trafficking and autophagy in Ugcg-deficient cardiomyocytes. We also showed that responsiveness to β-adrenergic stimulation was reduced in cardiomyocytes from hUgcg-/- mice and that Ugcg knockdown suppressed the internalization and trafficking of β1-adrenergic receptors.CONCLUSIONS: Our findings suggest that cardiac glycosphingolipids are required to maintain β-adrenergic signalling and contractile capacity in cardiomyocytes and to preserve normal heart function.
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| 4. |
- Falchenberg, Åsa, et al.
(författare)
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Emergency care at home - care that limps
- 2023
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Ingår i: Emergency Care Delivery at Home – An innovative approach for taking care of patients needs for emergency care.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: The number of patients who perceive themselves to have need for emergency care needs has increased over time. Some of these care needs can be addressed at patients' home (1). Emergency care delivery at home can be better for some patients (2). This arises questions how to provide high-quality and cost-effective emergency care (3). Therefore, it is needed to explore how delivery models can be changed for taking care of patients needs for emergency care. Aim: To explore emergency health care professionals’ experiences in caring for patients with emergency care needs in their homes.Methods: A qualitative study based on observations and interviews was used. Data was analyzed by content analysis. Results: No results are currently available as data collection is ongoing. The poster will present preliminary results at the conference. Conclusion: The findings can be assumed to contribute and stimulate to a continued discussion and development of new and additional models of emergency care delivery based on patient’s emergency care needs.
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| 5. |
- Falchenberg, Åsa, et al.
(författare)
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Emergency Care Delivery at Home – An innovative approach for taking care of patients needs for emergency care
- 2023
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Ingår i: Emergency Care Delivery at Home – An innovative approach for taking care of patients needs for emergency care.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: The number of patients who perceive themselves to have need for emergency care needs has increased over time. Some of these care needs can be addressed at patients' home (1). Emergency care delivery at home can be better for some patients (2). This arises questions how to provide high-quality and cost-effective emergency care (3). Therefore, it is needed to explore how delivery models can be changed for taking care of patients needs for emergency care. Aim: To explore emergency health care professionals’ experiences in caring for patients with emergency care needs in their homes.Methods: A qualitative study based on observations and interviews was used. Data was analyzed by content analysis. Results: No results are currently available as data collection is ongoing. The poster will present preliminary results at the conference. Conclusion: The findings can be assumed to contribute and stimulate to a continued discussion and development of new and additional models of emergency care delivery based on patient’s emergency care needs.
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| 6. |
- Kilbo Edlund, Karl, et al.
(författare)
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Long-term ambient air pollution and coronary atherosclerosis : results from the Swedish SCAPIS study
- 2024
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Ingår i: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484.
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Despite firm evidence for an association between long-term ambient air pollution exposure and cardiovascular morbidity and mortality, results from epidemiological studies on the association between air pollution exposure and atherosclerosis have not been consistent. We investigated associations between long-term low-level air pollution exposure and coronary atherosclerosis.Methods: We performed a cross-sectional analysis in the large Swedish CArdioPulmonary bioImaging Study (SCAPIS, n = 30 154), a random general population sample. Concentrations of total and locally emitted particulate matter <2.5 μm (PM2.5), <10 μm (PM10), and nitrogen oxides (NOx) at the residential address were modelled using high-resolution dispersion models. We estimated associations between air pollution exposures and segment involvement score (SIS), coronary artery calcification score (CACS), number of non-calcified plaques (NCP), and number of significant stenoses, using ordinal regression models extensively adjusted for potential confounders.Results: Median 10-year average PM2.5 exposure was 6.2 μg/m3 (range 3.5–13.4 μg/m3). 51 % of participants were women and 51 % were never-smokers. None of the assessed pollutants were associated with a higher SIS or CACS. Exposure to PM2.5 was associated with NCP (adjusted OR 1.34, 95 % CI 1.13, 1.58, per 2.05 μg/m3). Associations with significant stenoses were inconsistent.Conclusions: In this large, middle-aged general population sample with low exposure levels, air pollution was not associated with measures of total burden of coronary atherosclerosis. However, PM2.5 appeared to be associated with a higher prevalence of non-calcified plaques. The results suggest that increased risk of early-stage atherosclerosis or rupture, but not increased total atherosclerotic burden, may be a pathway for long-term air pollution effects on cardiovascular disease.
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| 7. |
- Kilbo Edlund, Karl, et al.
(författare)
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Long-term ambient air pollution and coronary atherosclerosis: Results from the Swedish SCAPIS study.
- 2024
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Ingår i: Atherosclerosis. - 1879-1484.
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Tidskriftsartikel (refereegranskat)abstract
- Despite firm evidence for an association between long-term ambient air pollution exposure and cardiovascular morbidity and mortality, results from epidemiological studies on the association between air pollution exposure and atherosclerosis have not been consistent. We investigated associations between long-term low-level air pollution exposure and coronary atherosclerosis.We performed a cross-sectional analysis in the large Swedish CArdioPulmonary bioImaging Study (SCAPIS, n=30154), a random general population sample. Concentrations of total and locally emitted particulate matter <2.5μm (PM2.5), <10μm (PM10), and nitrogen oxides (NOx) at the residential address were modelled using high-resolution dispersion models. We estimated associations between air pollution exposures and segment involvement score (SIS), coronary artery calcification score (CACS), number of non-calcified plaques (NCP), and number of significant stenoses, using ordinal regression models extensively adjusted for potential confounders.Median 10-year average PM2.5 exposure was 6.2μg/m3 (range 3.5-13.4μg/m3). 51% of participants were women and 51% were never-smokers. None of the assessed pollutants were associated with a higher SIS or CACS. Exposure to PM2.5 was associated with NCP (adjusted OR 1.34, 95% CI 1.13, 1.58, per 2.05μg/m3). Associations with significant stenoses were inconsistent.In this large, middle-aged general population sample with low exposure levels, air pollution was not associated with measures of total burden of coronary atherosclerosis. However, PM2.5 appeared to be associated with a higher prevalence of non-calcified plaques. The results suggest that increased risk of early-stage atherosclerosis or rupture, but not increased total atherosclerotic burden, may be a pathway for long-term air pollution effects on cardiovascular disease.
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| 8. |
- Morén, Björn, 1987-, et al.
(författare)
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Technical note: evaluation of a spatial optimization model for prostate high dose‐rate brachytherapy in a clinical treatment planning system
- 2023
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Ingår i: Medical physics (Lancaster). - : WILEY. - 0094-2405 .- 2473-4209. ; 50:2, s. 688-693
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSpatial properties of a dose distribution, such as volumes of contiguous hot spots, are of clinical importance in treatment planning for high dose-rate brachytherapy (HDR BT). We have in an earlier study developed an optimization model that reduces the prevalence of contiguous hot spots by modifying a tentative treatment plan. PurposeThe aim of this study is to incorporate the correction of hot spots in a standard inverse planning workflow and to validate the integrated model in a clinical treatment planning system. The spatial function is included in the objective function for the inverse planning, as opposed to in the previous study where it was applied as a separate post-processing step. Our aim is to demonstrate that fine-adjustments of dose distributions, which are often performed manually in todays clinical practice, can be automated. MethodsA spatial optimization function was introduced in the treatment planning system RayStation (RaySearch Laboratories AB, Stockholm, Sweden) via a research interface. A series of 10 consecutive prostate patients treated with HDR BT was retrospectively replanned with and without the spatial function. ResultsOptimization with the spatial function decreased the volume of the largest contiguous hot spot by on average 31%, compared to if the function was not included. The volume receiving at least 200% of the prescription dose decreased by on average 11%. Target coverage, measured as the fractions of the clinical target volume (CTV) and the planning target volume (PTV) receiving at least the prescription dose, was virtually unchanged (less than a percent change for both metrics). Organs-at-risk received comparable or slightly decreased doses if the spatial function was included in the optimization model. ConclusionsOptimization of spatial properties such as the volume of contiguous hot spots can be integrated in a standard inverse planning workflow for brachytherapy, and need not be conducted as a separate post-processing step.
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| 9. |
- Nydahl, Helena, 1990-
(författare)
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Communication of life cycle assessment results : life cycle key performance indicators
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The global warming that we are on track for will result in a severe loss of natural capital leading to significant losses in economic capital when urban infrastructure is destroyed, agricultural productivity declines and poverty spread among other disasters. Climate change due to emissions does not only affect the polluter, the hazardous effects becomes evident on a global level. An essential tool to enable decision‑making with concern to the welfare of the global commons is life cycle assessment (LCA). LCA compile and evaluate the inputs, outputs, and potential environmental impacts of a product system throughout its life cycle. The reviewed literature frames a gap regarding interpretation of LCA-results and inquire for guidelines that address a wide range of stakeholders to enable informed decision-making with regard to the welfare of the global commons. Some studies even argue that an apparent weakness of LCA-result communication is the understanding of what the results mean for the economic key performance indicators (KPIs) of the stakeholder. Thus, this thesis aims to contribute to the development of guidelines for interpretation of LCA-results by introducing an approach for communicating LCA-results that is compatible with the economically driven nature of stakeholders. The specific research questions (RQ) of this thesis are: (RQ1) How can well-established economic KPIs be utilised to quantify environmental impact? and (RQ2) How does incorporation of monetary valuation of environmental impacts and related environmental aspects affect the LCA-result and communication of results?These research questions have led to life cycle key performance indicators (LC‑KPIs) that quantify life cycle economic and environmental impacts in a way that take after the traditional economic KPIs of the stakeholders, which is outlined as essential to improve the understanding of LCA-results. The LC‑KPIs utilize the traditional economic KPIs of return on investment (ROI) and annual yield (AY). Additionally, to manage the large amount of non-commensurate units of holistic life cycle sustainability assessment, monetary valuation has been applied. Hence, contributing to the research area of monetary valuation in LCA by introducing and testing new approaches.The introduced LC-KPIs have been specified for building LCA and exemplified by applying them to a number of Swedish case buildings. The result show that the climate-economic assessment of building refurbishment differs compared to the traditional economic assessment when monetary valuation is utilized in LCA with the LC-KPI of ROIEconomy+. However, in the comparative assessment of building refurbishment and new construction, the LCA‑result does not change compared to the traditional economic assessment when monetary valuation is utilized in LCA with the LC-KPI of ELCCA. This is explained by the high costs associated with the investment and energy use of buildings and may not be the case if products with lower investment and energy use costs and high life cycle greenhouse-gas emissions would be studied. Still, if a purely environmental assessment of a product is wished for, the LC-KPI should only include monetary valuation of environmental impact factors and exclude traditional economic performance. Thus, the case study result defines further scope for research on the subject of monetary valuation in LCA and inquire for a wider spectrum of LC-KPIs that utilizes monetary valuation.The introduced approach of this thesis contribute to the development of guidelines for interpretation of LCA-results. Nevertheless, there are still challenges that needs to be addressed in the development of robust LCA-result interpretation. Still, the LC‑KPIs used in this thesis address the “cognitive logics” of a wide range of stakeholders and provide an approach for communication of LCA-results which improve the understanding of LCA-results.
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| 10. |
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