| 31. |
- Nahse, Viola, et al.
(författare)
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ATPase activity of DFCP1 controls selective autophagy
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The endoplasmic reticulum protein DFCP1 is found on omegasomes implicated in autophagosome biogenesis, but its function has remained unknown. Here, Nahse et al. show that DFCP1 is an ATPase that mediates selective autophagy by promoting constriction of large omegasomes. Cellular homeostasis is governed by removal of damaged organelles and protein aggregates by selective autophagy mediated by cargo adaptors such as p62/SQSTM1. Autophagosomes can assemble in specialized cup-shaped regions of the endoplasmic reticulum (ER) known as omegasomes, which are characterized by the presence of the ER protein DFCP1/ZFYVE1. The function of DFCP1 is unknown, as are the mechanisms of omegasome formation and constriction. Here, we demonstrate that DFCP1 is an ATPase that is activated by membrane binding and dimerizes in an ATP-dependent fashion. Whereas depletion of DFCP1 has a minor effect on bulk autophagic flux, DFCP1 is required to maintain the autophagic flux of p62 under both fed and starved conditions, and this is dependent on its ability to bind and hydrolyse ATP. While DFCP1 mutants defective in ATP binding or hydrolysis localize to forming omegasomes, these omegasomes fail to constrict properly in a size-dependent manner. Consequently, the release of nascent autophagosomes from large omegasomes is markedly delayed. While knockout of DFCP1 does not affect bulk autophagy, it inhibits selective autophagy, including aggrephagy, mitophagy and micronucleophagy. We conclude that DFCP1 mediates ATPase-driven constriction of large omegasomes to release autophagosomes for selective autophagy.
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| 32. |
- Simola, Saija, et al.
(författare)
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Patients’ Experiences of a National Patient Portal and Its Usability : Cross-Sectional Survey Study
- 2023
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Ingår i: Journal of Medical Internet Research. - : JMIR Publications. - 1438-8871. ; 25
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patient portals not only provide patients with access to electronic health records (EHRs) and other digital health services, such as prescription renewals, but they can also improve patients’ self-management, engagement with health care professionals (HCPs), and care processes. However, these benefits depend on patients’ willingness to use patient portals and, ultimately, their experiences with the usefulness and ease of use of the portals. Objective: This study aimed to investigate the perceived usability of a national patient portal and the relationship of patients’ very positive and very negative experiences with perceived usability. The study was aimed to be the first step in developing an approach for benchmarking the usability of patient portals in different countries. Methods: Data were collected through a web-based survey of the My Kanta patient portal’s logged-in patient users in Finland from January 24, 2022, to February 14, 2022. Respondents were asked to rate the usability of the patient portal, and the ratings were used to calculate approximations of the System Usability Scale (SUS) score. Open-ended questions asked the patients about their positive and negative experiences with the patient portal. The statistical analysis included multivariate regression, and the experience narratives were analyzed using inductive content analysis. Results: Of the 1,262,708 logged-in patient users, 4719 responded to the survey, giving a response rate of 0.37%. The patient portal’s usability was rated as good, with a mean SUS score of 74.3 (SD 14.0). Reporting a very positive experience with the portal was positively associated with perceived usability (β=.51; P<.001), whereas reporting a very negative experience was negatively associated with perceived usability (β=−1.28; P<.001). These variables explained 23% of the variation in perceived usability. The information provided and a lack of information were the most common positive and negative experiences. Furthermore, specific functionalities, such as prescription renewal and the ease of using the patient portal, were often mentioned as very positive experiences. The patients also mentioned negative emotions, such as anger and frustration, as part of their very negative experiences. Conclusions: The study offers empirical evidence about the significant role of individual experiences when patients are evaluating the usability of patient portals. The results suggest that positive and negative experiences provide relevant information that can be used for improving the patient portal’s usability. Usability should be improved so that patients receive information efficiently, easily, and quickly. Respondents would also appreciate interactive features in the patient portal.
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| 33. |
- Wang, Bo, et al.
(författare)
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Users’ Experiences With Online Access to Electronic Health Records in Mental and Somatic Health Care : Cross-Sectional Study
- 2023
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Ingår i: Journal of Medical Internet Research. - : JMIR Publications. - 1438-8871. ; 25
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patient-accessible electronic health records (PAEHRs) hold promise for empowering patients, but their impact may vary between mental and somatic health care. Medical professionals and ethicists have expressed concerns about the potential challenges of PAEHRs for patients, especially those receiving mental health care. OBJECTIVE: This study aims to investigate variations in the experiences of online access to electronic health records (EHRs) among persons receiving mental and somatic health care, as well as to understand how these experiences and perceptions vary among those receiving mental health care at different levels of point of care. METHODS: Using Norwegian data from the NORDeHEALTH 2022 Patient Survey, we conducted a cross-sectional descriptive analysis of service use and perceptions of perceived mistakes, omissions, and offensive comments by mental and somatic health care respondents. Content analysis was used to analyze free-text responses to understand how respondents experienced the most serious errors in their EHR. RESULTS: Among 9505 survey participants, we identified 2008 mental health care respondents and 7086 somatic health care respondents. A higher percentage of mental health care respondents (1385/2008, 68.97%) reported that using PAEHR increased their trust in health care professionals compared with somatic health care respondents (4251/7086, 59.99%). However, a significantly larger proportion (P<.001) of mental health care respondents (976/2008, 48.61%) reported perceiving errors in their EHR compared with somatic health care respondents (1893/7086, 26.71%). Mental health care respondents also reported significantly higher odds (P<.001) of identifying omissions (758/2008, 37.75%) and offensive comments (729/2008, 36.3%) in their EHR compared with the somatic health care group (1867/7086, 26.35% and 826/7086, 11.66%, respectively). Mental health care respondents in hospital inpatient settings were more likely to identify errors (398/588, 67.7%; P<.001) and omissions (251/588, 42.7%; P<.001) than those in outpatient care (errors: 422/837, 50.4% and omissions: 336/837, 40.1%; P<.001) and primary care (errors: 32/100, 32% and omissions: 29/100, 29%; P<.001). Hospital inpatients also reported feeling more offended (344/588, 58.5%; P<.001) by certain content in their EHR compared with respondents in primary (21/100, 21%) and outpatient care (287/837, 34.3%) settings. Our qualitative findings showed that both mental and somatic health care respondents identified the most serious errors in their EHR in terms of medical history, communication, diagnosis, and medication. CONCLUSIONS: Most mental and somatic health care respondents showed a positive attitude toward PAEHRs. However, mental health care respondents, especially those with severe and chronic concerns, expressed a more critical attitude toward certain content in their EHR compared with somatic health care respondents. A PAEHR can provide valuable information and foster trust, but it requires careful attention to the use of clinical terminology to ensure accurate, nonjudgmental documentation, especially for persons belonging to health care groups with unique sensitivities.
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| 34. |
- Adel Fahmideh, Maral, et al.
(författare)
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A Weighted Genetic Risk Score of Adult Glioma Susceptibility Loci Associated with Pediatric Brain Tumor Risk.
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic risk score (GRS) is used to demonstrate the genetic variants contributing to the polygenic architecture of complex diseases. By using a GRS, we have investigated the additive impact of the known adult glioma susceptibility loci on the pediatric brain tumor (PBT) risk and assessed the proportion of PBT heritability attributable to these susceptibility loci. A GRS was generated for PBTs based on the alleles and associated effect sizes derived from a previously published genome-wide association study on adult glioma. The GRS was calculated in CEFALO, a population-based case-control study of brain tumors in children and adolescents including saliva DNA of 245 cases and 489 controls. The unconditional logistic regression model was used to investigate the association between standardized GRS and risk of PBTs. To measure the variance explained by the effect of GRS, Nagelkerke pseudo-R2 was calculated. The GRS for adult brain tumors was associated with an increased risk of PBTs (OR 1.25 [95% CI 1.06-1.49], p = 0.009) and 0.3% of the variance in PBTs could be explained by the effect of GRS on the liability scale. This study provides evidence that heritable risks of PBTs are in-part attributable to some common genetic variants associated with adult glioma.
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| 35. |
- Adel Fahmideh, Maral, et al.
(författare)
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Common genetic variations in cell cycle and DNA repair pathways associated with pediatric brain tumor susceptibility
- 2016
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Ingår i: Oncotarget. - Stockholm : Karolinska Institutet, Institute of Environmental Medicine. - 1949-2553.
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge on the role of genetic polymorphisms in the etiology of pediatric brain tumors (PBTs) is limited. Therefore, we investigated the association between single nucleotide polymorphisms (SNPs), identified by candidate gene-association studies on adult brain tumors, and PBT risk. The study is based on the largest series of PBT cases to date. Saliva DNA from 245 cases and 489 controls, aged 7–19 years at diagnosis/reference date, was genotyped for 68 SNPs. Data were analyzed using unconditional logistic regression. The results showed EGFRrs730437 and EGFRrs11506105 may decrease susceptibility to PBTs, whereas ERCC1rs3212986 may increase risk of these tumors. Moreover, stratifid analyses indicated CHAF1Ars243341, CHAF1Ars2992, and XRCC1rs25487 were associated with a decreased risk of astrocytoma subtype. Furthermore, an increased risk of non-astrocytoma subtype associated with EGFRrs9642393, EME1rs12450550, ATMrs170548, and GLTSCRrs1035938 as well as a decreased risk of this subtype associated with XRCC4rs7721416 and XRCC4rs2662242 were detected. This study indicates SNPs in EGFR, ERCC1, CHAF1A, XRCC1, EME1, ATM, GLTSCR1, and XRCC4 may be associated with the risk of PBTs. Therefore, cell cycle and DNA repair pathways variations associated with susceptibility to adult brain tumors also seem to be associated with PBT risk, suggesting pediatric and adult brain tumors might share similar etiological pathways.
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| 36. |
- Agrell, Beata, et al.
(författare)
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Ett laglöst tillstånd
- 2012
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Annan publikation (populärvet., debatt m.m.)
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| 37. |
- Ahlbeck, Lars, 1964-, et al.
(författare)
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Intralymphatic immunotherapy with one or two allergens renders similar clinical response in patients with allergic rhinitis due to birch and grass pollen
- 2022
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Ingår i: Clinical and Experimental Allergy. - Chichester, United Kingdom : Wiley-Blackwell Publishing Inc.. - 0954-7894 .- 1365-2222. ; 52:6, s. 747-759
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionThere is a need for a fast, efficient and safe way to induce tolerance in patients with severe allergic rhinitis. Intralymphatic immune therapy has been shown to be effective. MethodsPatients with severe birch and timothy allergy were randomized and received three doses of 0.1 ml of birch and 5-grass allergen extracts (10,000 SQ units/ml, ALK-Abello), or birch and placebo or 5-grass and placebo by ultrasound-guided injections into inguinal lymph nodes at monthly intervals. Rhinoconjunctivitis total symptom score, medication score and rhinoconjunctivitis quality of life questionnaire were evaluated before treatment and after each birch and grass pollen season during three subsequent years. Circulating proportions of T helper subsets and allergen-induced cytokine and chemokine production were analysed by flow cytometry and Luminex.Results The three groups reported fewer symptoms, lower use of medication and improved quality of life during the birch and grass pollen seasons each year after treatment at an almost similar rate independently of treatment with one or two allergens. Mild local pain was the most common adverse event. IgE levels to birch decreased, whereas birch-induced IL-10 secretion increased in all three groups. IgG4 levels to birch and timothy and skin prick test reactivity remained mainly unchanged. Conjunctival challenge tests with timothy extract showed a higher threshold for allergen. In all three groups, regulatory T cell frequencies were increased 3 years after treatment.Conclusions Intralymphatic immunotherapy with one or two allergens in patients with grass and birch pollen allergy was safe, effective and may be associated with bystander immune modulatory responses.
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| 38. |
- Ahlbom, Anders, et al.
(författare)
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Occupational magnetic field exposure and myocardial infarction incidence.
- 2004
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Ingår i: Epidemiology. - : Ovid Technologies (Wolters Kluwer Health). - 1044-3983 .- 1531-5487. ; 15:4, s. 403-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Studies on healthy volunteers have seen reduced heart rate variability after exposure to extremely low-frequency electric and magnetic fields (EMF). Because reduced heart rate variability has been linked to cardiovascular disease risk, it has been hypothesized that exposure to EMF might increase the risk of cardiovascular disease. One epidemiologic study has shown increased mortality from cardiovascular conditions in utility workers with elevated exposure to magnetic fields, but several other epidemiologic studies have failed to confirm this result. We tested the hypothesis that occupational EMF exposure increases the risk of myocardial infarction in a large population-based case-control study of myocardial infarction, with detailed information on potential confounders. METHODS: We used data from the SHEEP study, which is a population-based case-control study of acute myocardial infarction in Stockholm. Occupational EMF exposure was based on job titles 1, 5, and 10 years before diagnosis. We used 2 approaches to classify exposure: first, specific individual job titles with presumed elevated EMF exposure, and second, classification of subjects according to a job-exposure matrix. RESULTS: We found no increased risk of myocardial infarction in subjects classified as having elevated EMF exposure. For the highest exposure category of > or = 0.3 microT according to the job-exposure matrix, the adjusted relative risk was = 0.57 (95% confidence interval = 0.36-0.89). CONCLUSIONS: The results of this study do not support the hypothesis that occupational EMF exposure increases the risk of myocardial infarction.
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| 39. |
- Aktaa, Suleman, et al.
(författare)
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European Society of Cardiology Quality Indicators for the care and outcomes of cardiac pacing : developed by the Working Group for Cardiac Pacing Quality Indicators in collaboration with the European Heart Rhythm Association of the European Society of Cardiology
- 2022
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 24:1, s. 165-172
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To develop a suite of quality indicators (QIs) for the evaluation of the care and outcomes for adults undergoing cardiac pacing.METHODS AND RESULTS: Under the auspice of the Clinical Practice Guideline Quality Indicator Committee of the European Society of Cardiology (ESC), the Working Group for cardiac pacing QIs was formed. The Group comprised Task Force members of the 2021 ESC Clinical Practice Guidelines on Cardiac Pacing and Cardiac Resynchronization Therapy, members of the European Heart Rhythm Association, international cardiac device experts, and patient representatives. We followed the ESC methodology for QI development, which involved (i) the identification of the key domains of care by constructing a conceptual framework of the management of patients receiving cardiac pacing, (ii) the development of candidate QIs by conducting a systematic review of the literature, (iii) the selection of the final set of QIs using a modified-Delphi method, and (iv) the evaluation of the feasibility of the developed QIs. Four domains of care were identified: (i) structural framework, (ii) patient assessment, (iii) pacing strategy, and (iv) clinical outcomes. In total, seven main and four secondary QIs were selected across these domains and were embedded within the 2021 ESC Guidelines on Cardiac Pacing and Cardiac Resynchronization therapy.CONCLUSION: By way of a standardized process, 11 QIs for cardiac pacing were developed. These indicators may be used to quantify adherence to guideline-recommended clinical practice and have the potential to improve the care and outcomes of patients receiving cardiac pacemakers.
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| 40. |
- Allentoft, Morten E., et al.
(författare)
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100 ancient genomes show repeated population turnovers in Neolithic Denmark
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625, s. 329-337
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Tidskriftsartikel (refereegranskat)abstract
- Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1–4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5–7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.
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