| 1. |
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| 2. |
- Hartmann, Miriam, et al.
(author)
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Associations between psychosocial wellbeing and experience of gender-based violence at community, household, and intimate-partner levels among a cross-sectional cohort of young people living with and without HIV during COVID-19 in Cape Town, South Africa
- 2023
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In: BMC Public Health. - : BioMed Central (BMC). - 1471-2458. ; 23:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Growing evidence indicates that gender-based violence (GBV) increased during COVID-19. We investigated self-reported impact of the pandemic on GBV at community, household and intimate partner (IPV) levels among young people and its associations with psychosocial wellbeing, i.e., COVID-related stressors and mental health.METHODS: Cross-sectional data were drawn from a survey with young people ages 13-24 (N = 536) living with HIV (YPLWH) and without HIV (YPLWoH), in peri-urban Cape Town, South Africa. The survey, conducted February-October 2021, examined the impact of the initial lockdown on experience and perceived changes in GBV at each level, and pandemic-related psychosocial wellbeing. Descriptive statistics and binomial and multinomial regression analyses were conducted to illustrate exposure and perceived changes in GBV since lockdown, and their association with COVID-related stress factors (e.g., social isolation, anxiety about COVID), mental health (e.g., depression, anxiety), and other risk factors (e.g., age, gender, socioeconomic status) by HIV status.RESULTS: Participants were 70% women with mean age 19 years; 40% were living with HIV. Since lockdown, YPLWoH were significantly more likely than YPLWH to perceive community violence as increasing (45% vs. 28%, p < 0.001), and to report household violence (37% vs. 23%, p = 0.006) and perceive it as increasing (56% vs. 27%, p = 0.002) (ref: decreasing violence). YPLWoH were also more likely to report IPV experience (19% vs. 15%, p = 0.41) and perception of IPV increasing (15% vs. 8%, p = 0.92). In adjusted models, COVID-related stressors and common mental health disorders were only associated with household violence. However, indicators of economic status such as living in informal housing (RRR = 2.07; 95% CI = 1.12-3.83) and food insecurity (Community violence: RRR = 1.79; 95% CI = 1.00-3.20; Household violence: RRR = 1.72; 95% CI = 1.15-2.60) emerged as significant risk factors for exposure to increased GBV particularly among YPLWoH.CONCLUSIONS: Findings suggest that for young people in this setting, GBV at community and household levels was more prevalent during COVID-19 compared to IPV, especially for YPLWoH. While we found limited associations between COVID-related stressors and GBV, the perceived increases in GBV since lockdown in a setting where GBV is endemic, and the association of household violence with mental health, is a concern for future pandemic responses and should be longitudinally assessed.
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| 3. |
- Ludvigsson, Jonas F., 1969-, et al.
(author)
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Adaptation of the Charlson Comorbidity Index for Register-Based Research in Sweden
- 2021
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In: Clinical Epidemiology. - : Dove Medical Press Ltd.. - 1179-1349. ; 13, s. 21-41
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Journal article (peer-reviewed)abstract
- Purpose: Comorbidity indices are often used to measure comorbidities in register-based research. We aimed to adapt the Charlson comorbidity index (CCI) to a Swedish setting.Methods: Four versions of the CCI were compared and evaluated by disease-specific experts.Results: We created a cohesive coding system for CCI to 1) harmonize the content between different international classification of disease codes (ICD-7,8,9,10), 2) delete incorrect codes, 3) enhance the distinction between mild, moderate or severe disease (and between diabetes with and without end-organ damage), 4) minimize duplication of codes, and 5) briefly explain the meaning of individual codes in writing.Conclusion: This work may provide an integrated and efficient coding algorithm for CCI to be used in medical register-based research in Sweden.
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| 4. |
- Alfvén, Tobias, et al.
(author)
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Agenda 2030 och målen för en hållbar utveckling angår oss alla
- 2020
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In: Läkartidningen. - 0023-7205. ; 117
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Journal article (peer-reviewed)abstract
- The 2030 Agenda for Sustainable Development and its seventeen Sustainable Development Goals were adopted by the United Nations General Assembly in 2015. It is a bold agenda for global social, environmental and economic development, with human health as a central theme. Even though substantial improvements in health have been achieved during the last decades, every year over 5 million children die, mostly from preventable causes, and 300 000 women die in conjunction with childbirth. Premature deaths from non-communicable diseases are increasing, and our ability to treat infections is under threat through widespread anti-microbial resistance. Climate change is recognized as the biggest threat to health in our time. When the world now starts to plan for how society and our health systems should be reorganized after the COVID-19 pandemic the 2030 Agenda could and should play a central role. In this context, Agenda 2030 provides an ambitious roadmap for development, with its emphasis on collaboration across borders and disciplines. The agenda is achievable but reaching its goals will require strong commitment at all levels and societal change on a large scale.
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| 5. |
- Alfvén, Tobias, et al.
(author)
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Agenda 2030 och målen för en hållbar utveckling angår oss alla [The 2030 Agenda for Sustainable Development - an important opportunity to improve global health]
- 2020
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In: Läkartidningen. - : Sveriges Läkarförbund. - 0023-7205 .- 1652-7518. ; 117
-
Research review (peer-reviewed)abstract
- The 2030 Agenda for Sustainable Development and its seventeen Sustainable Development Goals were adopted by the United Nations General Assembly in 2015. It is a bold agenda for global social, environmental and economic development, with human health as a central theme. Even though substantial improvements in health have been achieved during the last decades, every year over 5 million children die, mostly from preventable causes, and 300 000 women die in conjunction with childbirth. Premature deaths from non-communicable diseases are increasing, and our ability to treat infections is under threat through widespread anti-microbial resistance. Climate change is recognized as the biggest threat to health in our time. When the world now starts to plan for how society and our health systems should be reorganized after the COVID-19 pandemic the 2030 Agenda could and should play a central role. In this context, Agenda 2030 provides an ambitious roadmap for development, with its emphasis on collaboration across borders and disciplines. The agenda is achievable but reaching its goals will require strong commitment at all levels and societal change on a large scale.
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| 6. |
- Alhamdow, Ayman, et al.
(author)
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Low-level exposure to polycyclic aromatic hydrocarbons is associated with reduced lung function among Swedish young adults
- 2021
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In: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 197
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Journal article (peer-reviewed)abstract
- Background: Exposure to polycyclic aromatic hydrocarbons (PAHs) has been linked to adverse pulmonary effects. However, the impact of low-level environmental PAH exposure on lung function in early adulthood remains uncertain. Objectives: To evaluate the associations between urinary PAH metabolites and lung function parameters in young adults. Methods: Urinary metabolites of pyrene, phenanthrene, and fluorene were analysed in 1000 young adults from Sweden (age 22–25 years) using LC-MS/MS. Lung function and eosinophilic airway inflammation were measured by spirometry and exhaled nitric oxide fraction (FeNO), respectively. Linear regression analysis was used to evaluate associations between PAH metabolites and the outcomes. Results: Median urinary concentrations of 1-OH-pyrene, ∑OH-phenanthrene, and ∑OH-fluorene were 0.066, 0.36, 0.22 μg/L, respectively. We found inverse associations of ∑OH-phenanthrene and ∑OH-fluorene with FEV1 and FVC, as well as between 1-OH-pyrene and FEV1/FVC ratio (adjusted P < 0.05; all participants). An increase of 1% in ∑OH-fluorene was associated with a decrease of 73 mL in FEV1 and 59 mL in FVC. In addition, ∑OH-phenanthrene concentrations were, in a dose-response manner, inversely associated with FEV1 (B from −109 to −48 compared with the lowest quartile of ∑OH-phenanthrene; p trend 0.004) and FVC (B from −159 to −102 compared with lowest quartile; p-trend <0.001). Similar dose-response associations were also observed between ∑OH-fluorene and FEV1 and FVC, as well as between 1-OH-pyrene and FEV1/FVC (p-trend <0.05). There was no association between PAH exposure and FeNO, nor was there an interaction with smoking, sex, or asthma. Conclusion: Low-level PAH exposure was, in a dose-response manner, associated with reduced lung function in young adults. Our findings have public health implications due to i) the widespread occurrence of PAHs in the environment and ii) the clinical relevance of lung function in predicting all-cause and cardiovascular disease mortality.
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| 7. |
- Axelsson, Mette, et al.
(author)
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Mat vid diabetes. : En systematisk översikt med utvärdering av effekter samt hälsoekonomiska och etiska aspekter.
- 2022
-
Reports (other academic/artistic)abstract
- SlutsatserTyp 1- och typ 2-diabetes Det finns ett samband mellan att äta medelhavskost och lägre risk att dö i förtid oavsett orsak (måttlig tillförlitlighet). Det finns ett samband mellan att äta en större andel2 fibrer eller baljväxter och lägre risk att dö i förtid oavsett orsak (måttlig tillförlitlighet). Det kan även finnas ett samband mellan att äta en större andel nötter och lägre risk att dö i förtid oavsett orsak (låg tillförlitlighet) samt lägre risk att insjukna i hjärt- och kärlsjukdom (låg tillförlitlighet). Det finns ett samband mellan att dricka mer2 kaffe och lägre risk att dö i förtid oavsett orsak och lägre risk att dö i förtid i kranskärlssjukdom (måttlig tillförlitlighet) samt möjligen en lägre risk att dö i förtid i hjärt- och kärlsjukdom (låg tillförlitlighet). Det råder generell brist på studier med lång uppföljningstid som jämför inverkan av olika slags kostråd på överlevnad, diabeteskomplikationer, diabetesremission3, livskvalitet och biverkningar. Tillförlitligheten av befintliga resultat är dessutom mycket låg för de flesta koster, kostbehandlingar, livsmedel och näringsämnen som har utvärderats. Effekter på hälsa och relaterade mått kan i dessa fall inte bedömas.2. Begreppet ”större andel” eller ”mer” avser inte nödvändigtvis att äta eller dricka mer totalt utan att öka mängden av ett visst livsmedel genom att byta ut annan mat eller dryck.Typ 2-diabetes Det kan finnas ett samband mellan att äta en större andel mättat fett och högre risk för att dö i förtid av hjärt- och kärlsjukdom (låg tillförlitlighet). Det kan även finnas ett samband mellan att äta en större andel enkelomättat fett och lägre risk att dö i förtid oavsett orsak (låg tillförlitlighet). En behandling med en initial period av kraftigt minskat energiintag med hjälp av lågenergipulver (VLED) med efterföljande övergång till mat för viktstabilitet jämfört med vanlig kostbehandling har gynnsamma effekter på livskvalitet (enligt EQ-5D), långtidsblodsocker (HbA1c) och vikt upp till 12 månader (måttlig tillförlitlighet)4. Vidare kan metoder där VLED ingår ha gynnsamma effekter på diabetesremission5 och midjeomfång upp till 12 månader (låg tillförlitlighet) och långtidsblodsocker (HbA1c) upp till 24 månader (låg tillförlitlighet). Intensiv livsstilsbehandling därlågfettkost kombineras med fysisk aktivitet och minskat energiintag har gynnsamma effekter jämfört med vanlig kostbehandling på långtidsblodsocker (HbA1c), vikt, kroppsmasseindex (BMI), midjeomfång och vissa blodfetter upp till 12 månader (måttlig tillförlitlighet)3. Viktminskningen kan kvarstå upp till omkring 10 år (låg tillförlitlighet). Behandlingen kan leda till bättre fysisk livskvalitet upp till 8 år (låg tillförlitlighet) medan effektskillnaden i psykisk livskvalitet under samma tid kan vara obefintlig eller försumbar (låg tillförlitlighet). Jämförelsen påvisar ingen förändrad risk att dö i förtid oavsett orsak eller att dö eller insjukna av kardiovaskulära orsaker efter omkring 10 år (låg tillförlitlighet). I det hälsoekonomiska perspektivet är intensiv livsstilsbehandling mer resurskrävande än vanlig kostbehandling, och beräkningar visar små eller inga vinster i kvalitetsjusterade levnadsår (QALYs) på individnivå. Energirestriktion i samband med intensiv livsstilsbehandling med ketogen kost eller med högproteinkost (20 E%) i kombination med fysisk aktivitet jämfört med vanlig kostbehandling kan ge en viktminskning upp till 11 månader (låg tillförlitlighet) men det saknas studier som kan visa om vikten kan bibehållas på längre sikt. Det saknas studier som undersökt kliniskt viktiga utfall som dödlighet, kardiovaskulära sjukdomar, livskvalitet och diabetesremission.3. Gäller endast vid typ 2-diabetes.4. Utgår från individer med en medelkroppsvikt på cirka 100 kg och medel-HbA1c på 60 mmol/mol.5. Resultaten för utfallet diabetesremission (att uppnå normala blodsockervärden) gäller när en diabetesdiagnos sattes för mindre än 6 år sedan eller för mindre än 3 år sedan. Definitionen för diabetesremission var ett HbA1c på mindre än 48 mmol/mol och att samtidigt vara fri från blodsockersänkande läkemedel.Graviditetsdiabetes Det saknas studier om kost vid graviditetsdiabetes med tillräcklig tillförlitlighet för att kunna bedöma effekterna.
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| 8. |
- Causevic, Sara, 1981-, et al.
(author)
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Prevalence and associated factors for poor mental health among young migrants in Sweden : a cross-sectional study
- 2024
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In: Global Health Action. - : Taylor & Francis. - 1654-9716 .- 1654-9880. ; 17:1
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Journal article (peer-reviewed)abstract
- BACKGROUND Young migrants face multiple challenges that can affect their mental, sexual and reproductive health.OBJECTIVE To assess the prevalence of self-reported poor mental health and its associated demographic, post-migration and sexual risk behaviour factors among young migrants (aged 15–25) in Sweden.METHODS Data were drawn from a cross-sectional survey conducted with migrants aged 15–65 years old in Sweden between December 2018 and November 2019 (n = 6449). Among these, 990 participants aged 15–25 were eligible for the study. Mental health was measured using the Refugee Health Screener-13. Missing data indicator analysis and multivariable logistic regression models were conducted to estimate the association between mental health, sexual risk behaviour, demographic and migration-related variables.RESULTS Of the 990 participants, 59% reported poor mental health. Participants reporting poor mental health were more likely to be female (AOR:1.63, 95% CI:1.18–2.25), to have lived in Sweden more than three years (AOR:2.16, 95% CI:1.17–3.97), to engage in any sexual risk behaviour (AOR:1.99, 95% CI:1.25–3.17), and to live alone (AOR:1.95, 95% CI:1.25–3.03) or with friends they already knew (AOR:1.60, 95% CI:1.37–4.91). People arriving from the Americas (AOR:0.54, 95% CI:0.33–0.88), Asia (AOR:0.44, 95% CI:0.22–0.86), Europe (AOR:0.30, 95% CI:0.14–0.61) and Africa (AOR 0.37, 95% CI: 0.23–0.60) had lower odds of poor mental health than those arriving from Syria.CONCLUSION The prevalence of poor mental health among young migrants in Sweden was high, with specific subgroups (women, asylum seekers, people arriving from Syria, and those residing longer in Sweden) being particularly vulnerable. Our results indicate the interconnectedness between poor mental health and sexual risk behaviour in this population. Thus, policies targeting young migrants should ensure that healthcare services screen for both poor sexual and mental health at the same time.
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| 9. |
- Gusdal, Annelie K, 1963-, et al.
(author)
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Voices on adherence to ART in Ethiopia and Uganda : a matter of choice or simply not an option?
- 2009
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In: AIDS Care. - : Informa UK Limited. - 0954-0121 .- 1360-0451. ; 21:11, s. 1381-1387
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Journal article (peer-reviewed)abstract
- This paper explores HIV patients' adherence to antiretroviral treatment (ART) in resource-limited contexts in Uganda and Ethiopia, where ART is provided free of charge. Qualitative semi-structured interviews were conducted with 79 patients, 17 peer counselors, and 22 providers in ART facilities in urban and rural areas of Ethiopia and Uganda. Interviewees voiced their experiences of, and views on ART adherence both from an individual and a system level perspective. Two main themes emerged from the content analysis: "Patients' competing costs and systems' resource constraints'' and "Patients' trust in ART and quality of the patient-provider encounters.'' The first theme refers to how patients' adherence was challenged by difficulties in supporting themselves and their families, paying for transportation, for drug refill and follow-up as well as paying for registration fees, opportunistic infection treatment, and expensive referrals to other hospitals. The second theme describes factors that influenced patients' capacity to adhere: personal responsibility in treatment, trust in the effects of antiretroviral drugs, and trust in the quality of counseling. To grant patients a fair choice to successfully adhere to ART, transport costs to ART facilities need to be reduced. This implies providing patients with drugs for longer periods of time and arranging for better laboratory services, thus not necessitating frequent revisits. Services ought to be brought closer to patients and peripheral, community-based healthworkers used for drug distribution. There is a need for training providers and peer counselors, in communication skills and adherence counseling.
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| 10. |
- Lasaviciute, Gintare, 1990-, et al.
(author)
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Human Bone Marrow Mesenchymal Stromal Cell-Derived CXCL12, IL-6 and GDF-15 and Their Capacity to Support IgG-Secreting Cells in Culture Are Divergently Affected by Doxorubicin
- 2021
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In: Hemato. - : MDPI AG. - 2673-6357. ; 2:1, s. 154-166
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Journal article (peer-reviewed)abstract
- Various subsets of bone marrow mesenchymal stromal cells (BM MSCs), including fibroblasts, endothelial, fat and reticular cells, are implicated in the regulation of the hematopoietic microenvironment and the survival of long-lived antibody-secreting cells (ASCs). Nowadays it is widely acknowledged that vaccine-induced protective antibody levels are diminished in adults and children that are treated for hematological cancers. A reason behind this could be damage to the BM MSC niche leading to a diminished pool of ASCs. To this end, we asked whether cell cytotoxic treatment alters the capacity of human BM MSCs to support the survival of ASCs. To investigate how chemotherapy affects soluble factors related to the ASC niche, we profiled a large number of cytokines and chemokines from in vitro-expanded MSCs from healthy donors or children who were undergoing therapy for acute lymphoblastic leukemia (ALL), following exposure to a widely used anthracycline called doxorubicin (Doxo). In addition, we asked if the observed changes in the measured soluble factors after Doxo exposure impacted the ability of the BM niche to support humoral immunity by co-culturing Doxo-exposed BM MSCs with in vitro-differentiated ASCs from healthy blood donors, and selective neutralization of cytokines. Our in vitro results imply that Doxo-induced alterations in BM MSC-derived interleukin 6 (IL-6), CXCL12 and growth and differentiation factor 15 (GDF-15) are not sufficient to disintegrate the support of IgG-producing ASCs by the BM MSC niche, and that serological memory loss may arise during later stages of ALL therapy.
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| 11. |
- Litorp, Helena, 1980-, et al.
(author)
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Gender norms and women’s empowerment as barriers to facility birth : A population-based cross-sectional study in 26 Nigerian states using the World Values Survey
- 2022
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:8
-
Journal article (peer-reviewed)abstract
- BackgroundCentral and western Africa struggle with the world’s lowest regional proportion of facility birth at 57%. The aim of the current study was to compare beliefs related to maternal health care services, science/technology, gender norms, and empowerment in states with high vs. low proportions of facility birth in Nigeria.MethodsFace-to-face interviews were performed as part of a nationally representative survey in Nigeria using a new module to measure values and beliefs related to gender and sexual and reproductive health and rights collected as part the 2018 World Values Survey. We compared beliefs related to maternal health care services, science/technology, gender norms, and empowerment between Nigerian states with facility birth proportions > 50% vs. < 25% as presented in the 2018 Nigerian Demographic Health Survey report. Pearson’s chi-squared test, the independent t-test, and univariable and multivariable logistic and linear regression were used for analyses. Results were also stratified by gender.ResultsAmong the 1,273 participants interviewed, 653 resided in states with high and 360 resided in states with low proportions of facility birth. There were no significant differences between the groups in perceived safety of facility birth (96% vs. 94%) and confidence in antenatal care (91% vs 94%). However, in states with low proportions of facility birth, participants had higher confidence in traditional birth attendants (61% vs. 39%, adjusted odds ratio [aOR] 2.1, [1.5–2.8]), men were more often perceived as the ones deciding whether a woman should give birth at a clinic (56% vs. 29%, aOR 2.4 [1.8–3.3]), and participants experienced less freedom over their own lives (56% vs. 72%, aOR 0.56 [0.41–0.76]). Most differences in responses between men and women were not statistically significant.ConclusionsIn order to increase facility births in Nigeria and other similar contexts, transforming gender norms and increasing women’s empowerment is key.
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| 12. |
- Löfdahl, Anna, et al.
(author)
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5-HT2B receptor antagonists attenuate myofibroblast differentiation and subsequent fibrotic responses in vitro and in vivo
- 2016
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In: Physiological Reports. - : Wiley. - 2051-817X. ; 4:15
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Journal article (peer-reviewed)abstract
- Pulmonary fibrosis is characterized by excessive accumulation of connective tissue, along with activated extracellular matrix (ECM)-producing cells, myofibroblasts. The pathological mechanisms are not well known, however serotonin (5-HT) and 5-HT class 2 (5-HT2) receptors have been associated with fibrosis. The aim of the present study was to investigate the role of 5-HT2B receptors in fibrosis, using small molecular 5-HT2B receptor antagonists EXT5 and EXT9, with slightly different receptor affinity. Myofibroblast differentiation [production of alpha-smooth muscle actin (α-SMA)] and ECM synthesis were quantified in vitro, and the effects of the receptor antagonists were evaluated. Pulmonary fibrosis was also modeled in mice by subcutaneous bleomycin administrations (under light isoflurane anesthesia), and the effects of receptor antagonists on tissue density, collagen-producing cells, myofibroblasts and decorin expression were investigated. In addition, cytokine expression was analyzed in serum. Lung fibroblasts displayed an increased α-SMA (P < 0.05) and total proteoglycan production (P < 0.01) when cultured with TGF-β1 together with 5-HT, which were significantly reduced with both receptor antagonists. Following treatment with EXT5 or EXT9, tissue density, expression of decorin, number of collagen-producing cells, and myofibroblasts were significantly decreased in vivo compared to bleomycin-treated mice. Receptor antagonization also significantly reduced systemic levels of TNF-α and IL-1β, indicating a role in systemic inflammation. In conclusion, 5-HT2B receptor antagonists have potential to prevent myofibroblast differentiation, in vitro and in vivo, with subsequent effect on matrix deposition. The attenuating effects of 5-HT2B receptor antagonists on fibrotic tissue remodeling suggest these receptors as novel targets for the treatment of pulmonary fibrosis.
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| 13. |
- Smedby, Karin Ekström, et al.
(author)
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Ultraviolet radiation exposure and risk of malignant lymphomas
- 2005
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 97:3, s. 199-209
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The incidence of malignant lymphomas has been increasing rapidly, but the causes of these malignancies remain poorly understood. One hypothesis holds that exposure to ultraviolet (UV) radiation increases lymphoma risk. We tested this hypothesis in a population-based case-control study in Denmark and Sweden. METHODS: A total of 3740 patients diagnosed between October 1, 1999, and August 30, 2002, with incident malignant lymphomas, including non-Hodgkin lymphoma, chronic lymphocytic leukemia, and Hodgkin lymphoma, and 3187 population controls provided detailed information on history of UV exposure and skin cancer and information on other possible risk factors for lymphomas. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by logistic regression. Statistical tests were two-sided. RESULTS: Multivariable-adjusted analyses revealed consistent, statistically significant negative associations between various measures of UV light exposure and risk of non-Hodgkin lymphoma. A high frequency of sun bathing and sunburns at age 20 years and 5-10 years before the interview and sun vacations abroad were associated with 30%-40% reduced risks of non-Hodgkin lymphoma (e.g., for sunbathing four times a week or more at age 20 versus never sunbathing, OR = 0.7, 95% CI = 0.6 to 0.9; for two or more sunburns a year at age 20 versus no sunburns, OR = 0.6, 95% CI = 0.5 to 0.8). These inverse associations increased in strength with increasing levels of exposure (all P(trend)< or =.01). Similar, albeit weaker, associations were observed for Hodgkin lymphoma. There were no clear differences among non-Hodgkin lymphoma subtypes, although associations were stronger for B-cell than for T-cell lymphomas. A history of skin cancer was associated with a doubling in risks of both non-Hodgkin and Hodgkin lymphoma. CONCLUSIONS: A history of high UV exposure was associated with reduced risk of non-Hodgkin lymphoma. The positive association between skin cancer and malignant lymphomas is, therefore, unlikely to be mediated by UV exposure.
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| 14. |
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| 15. |
- Svallfors, Signe, et al.
(author)
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Armed conflict, insecurity, and attitudes toward women's and girls' reproductive autonomy in Nigeria
- 2024
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In: Social Science and Medicine. - : Elsevier. - 0277-9536 .- 1873-5347. ; 348
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Journal article (peer-reviewed)abstract
- Background: Armed conflict and insecurity have been linked to deteriorations in reproductive health and rights globally. In Nigeria, armed violence has taken a significant toll on women's and girls' health and safety. However, knowledge is limited about how conflict shapes attitudes surrounding their ability to make autonomous decisions on relationships and childbearing. Drawing on a socioecological framework and terror management theory, we aimed to investigate the association between conflict, insecurity, and attitudes toward women's and girls' reproductive autonomy in Nigeria.Methods: We conducted a cross-sectional study using data from two sources: the World Values Survey (WVS) and the Uppsala Conflict Data Program-Georeferenced Event Dataset (UCDP-GED). Nationally representative data on attitudes of 559 men and 534 women was collected by WVS in 2017-2018. Linear probability models estimated the association between attitudes toward five dimensions of women and girl's reproductive autonomy (contraception, safe abortion, marital decisionmaking, delayed childbearing, early marriage), respondents' perceptions of neighborhood insecurity using WVS data, and geospatial measures of conflict exposure drawn from UCDP-GED.Results: Exposure to armed conflict and perceived neighborhood insecurity were associated with more supportive attitudes toward access to safe abortion among both men and women. Among women, conflict exposure was associated with higher support for contraception and the perception that early marriage can provide girls with security. Conflict -affected men were more likely to support a delay in girls' childbearing.Conclusion: Our findings suggest that conflict and insecurity pose a threat to, but also facilitate opportunities for, women's and girls' reproductive autonomy. Contraception, abortion, early marriage, and postponement or childbearing may be perceived as risk -aversion strategies in response to mortality threats, livelihood losses, and conflict -driven sexual violence. Our findings foreshadow changes in fertility and relationship patterns in conflict -affected Nigeria and highlight the need for health programming to ensure access to contraception and safe abortion services.
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| 16. |
- Svallfors, Signe, et al.
(author)
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Support for sexual and reproductive health and rights in Sub-Saharan Africa : a new index based on World Values Survey data
- 2024
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In: Reproductive Health. - : BioMed Central (BMC). - 1742-4755. ; 21:1
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Journal article (peer-reviewed)abstract
- Background: Addressing attitudes is central to achieving sexual and reproductive health and rights (SRHR) and Agenda 2030. We aimed to develop a comprehensive index to measure attitudinal support for SRHR, expanding opportunities for global trend analyses and tailored interventions. Methods: We designed a new module capturing attitudes towards different dimensions of SRHR, collected via the nationally representative World Values Survey in Ethiopia, Kenya, and Zimbabwe during 2020–2021 (n = 3,711). We used exploratory factor analysis of 58 items to identify sub-scales and an overall index. Adjusted regression models were used to evaluate the index according to sociodemographic characteristics, stratified by country and sex. Results: A 23-item, five-factor solution was identified and used to construct sub-indices reflecting support for: (1) sexual and reproductive rights, (2) neighborhood sexual safety, (3) gender-equitable relationships, (4) equitable masculinity norms, and (5) SRHR interventions. These five sub-indices performed well across countries and socioeconomic subgroups and were combined into a comprehensive “SRHR Support Index”, standardized on a 1–100 scale (mean = 39.19, SD = 15.27, Cronbach’s alpha = 0.80) with higher values indicating more support for SRHR. Mean values were highest in Kenya (45.48, SD = 16.78) followed by Ethiopia (40.2, SD = 13.63), and lowest in Zimbabwe (32.65, SD = 13.77), with no differences by sex. Higher education and being single were associated with more support, except in Ethiopia. Younger age and urban residence correlated with more support among males only. Conclusion: The SRHR Support Index has the potential to broaden SRHR attitude research from a comprehensive perspective – addressing the need for a common measure to track progress over time.
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| 17. |
- Thorfve, Anna, 1982, et al.
(author)
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Gene Expression Profiling of Peri-Implant Healing of PLGA-Li+ Implants Suggests an Activated Wnt Signaling Pathway In Vivo
- 2014
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In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:7
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Journal article (peer-reviewed)abstract
- Bone development and regeneration is associated with the Wnt signaling pathway that, according to literature, can be modulated by lithium ions (Li+). The aim of this study was to evaluate the gene expression profile during peri-implant healing of poly(lactic-co-glycolic acid) (PLGA) implants with incorporated Li+, while PLGA without Li+ was used as control, and a special attention was then paid to the Wnt signaling pathway. The implants were inserted in rat tibia for 7 or 28 days and the gene expression profile was investigated using a genome-wide microarray analysis. The results were verified by qPCR and immunohistochemistry. Histomorphometry was used to evaluate the possible effect of Li+ on bone regeneration. The microarray analysis revealed a large number of significantly differentially regulated genes over time within the two implant groups. The Wnt signaling pathway was significantly affected by Li+, with approximately 34% of all Wnt-related markers regulated over time, compared to 22% for non-Li+ containing (control; Ctrl) implants. Functional cluster analysis indicated skeletal system morphogenesis, cartilage development and condensation as related to Li+. The downstream Wnt target gene, FOSL1, and the extracellular protein-encoding gene, ASPN, were significantly upregulated by Li+ compared with Ctrl. The presence of beta-catenin, FOSL1 and ASPN positive cells was confirmed around implants of both groups. Interestingly, a significantly reduced bone area was observed over time around both implant groups. The presence of periostin and calcitonin receptor-positive cells was observed at both time points. This study is to the best of the authors' knowledge the first report evaluating the effect of a local release of Li+ from PLGA at the fracture site. The present study shows that during the current time frame and with the present dose of Li+ in PLGA implants, Li+ is not an enhancer of early bone growth, although it affects the Wnt signaling pathway.
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| 18. |
- Tirado, Veronika, et al.
(author)
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"One-time interventions, it doesn't lead to much" : healthcare provider views to improving sexual and reproductive health services for young migrants in Sweden
- 2022
-
In: BMC Health Services Research. - : BioMed Central (BMC). - 1472-6963. ; 22:1
-
Journal article (peer-reviewed)abstract
- BackgroundSexual and reproductive health and rights (SRHR) is an important aspect for young people. In Sweden, young migrants often encounter barriers to accessing and using sexual and reproductive health (SRH) services, despite that these services are free of charge for young people (ages 15–25). Healthcare providers’ views and best practices are of great importance for improving the utilisation of existing SRH services, particularly for young people. This study aims to understand healthcare providers’ experiences and perspectives on barriers to SRHR among young migrants and their suggestions for strategies to improve the provision of SRH services to this group.MethodsMidwives, counsellors and nurses with at least five years of professional experience within SRHR were reached through a purposeful sample at primary care clinics, specialised clinics and youth-friendly clinics, which provide SRH services to migrant youths in Stockholm. Twelve interviews were conducted from May 2018 to February 2020. Qualitative content analysis was performed.ResultsThe analysis identified one theme: Improving the fragmentation in the SRH services, and four sub-themes: 1. Being unaware of SRHR; 2. Creating trust and responsive interactions; 3. Communicating in the same language; and 4. Collaborating to build bridges. The barriers included distrust in the healthcare system, socio-cultural norms surrounding SRHR, incomplete translations, and a need for long-lasting collaboration with SRH services and other range of services for migrants. The strategies for improvement as suggested by participants included involving existing cultural groups and organisations to enable trust, consistent and dependable interpreters, a streamline of SRH services with other healthcare staff and health facilities, and collaborations with homes designated for young migrants and language schools for a direct linkage to service providers.ConclusionsFindings indicate that there are fragmentations in SRH services, and these include lack of knowledge about SRHR among migrant youth, language and communication barriers, and a lack of structure needed to build dependable services that go beyond one-time interventions. While initiatives and strategies from healthcare providers for improvement of SRH services exist, the implementation of some strategies may also require involving the regional and national decision-makers and multi-stakeholders like communities, civil society and young migrants themselves.
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| 19. |
- Uhlén, Mathias, et al.
(author)
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A human protein atlas for normal and cancer tissues based on antibody proteomics
- 2005
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In: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 4:12, s. 1920-1932
-
Journal article (peer-reviewed)abstract
- Antibody-based proteomics provides a powerful approach for the functional study of the human proteome involving the systematic generation of protein-specific affinity reagents. We used this strategy to construct a comprehensive, antibody-based protein atlas for expression and localization profiles in 48 normal human tissues and 20 different cancers. Here we report a new publicly available database containing, in the first version, similar to 400,000 high resolution images corresponding to more than 700 antibodies toward human proteins. Each image has been annotated by a certified pathologist to provide a knowledge base for functional studies and to allow queries about protein profiles in normal and disease tissues. Our results suggest it should be possible to extend this analysis to the majority of all human proteins thus providing a valuable tool for medical and biological research.
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| 20. |
- Vadeby, Anna, 1969-, et al.
(author)
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Säker framkomlighet : sammanfattande slutrapport 2015
- 2016
-
Reports (other academic/artistic)abstract
- Föreliggande rapport redovisar övergripande resultat av fyra olika åtgärder som implementerats inomTrafikverkets projekt ”Säker framkomlighet” vilket haft som syfte att förbättra framkomlighet ochtrafiksäkerhet på främst befintliga tvåfältsvägar med hastighetsgräns 90 km/tim. Åtgärderna somstuderats är: frästa mitträfflor på 2-fältsvägar, vägrensräffling på motorväg, smala mötesfria vägar(”gles 2+1-väg med räcke”) och riktningsseparerade vägar (2+1 med målad/räfflad mitt).Resultaten visar att för samtliga åtgärder har trafiksäkerhetseffekterna varit positiva med minskningarav de dödade och svårt skadade trafikanterna. Vad gäller spårdjupstillväxt visar resultaten att mitträfflinginte har en kanaliserande effekt på trafiken och därmed påverkas inte heller spårbildningen.För mötesfria vägar är den årliga spårdjupsutvecklingen cirka 25 procent högre för mötesfri väg än förmotsvarande vanlig väg för årsdygnstrafik (ÅDT) > 8 000 fordon/dygn. För lägre ÅDT är skillnaden 10–15 procent.För riktningsseparerade vägar visar resultaten endast på högre spårdjupstillväxt för ÅDT över 8 000fordon/dygn. En studie om effekter och konsekvenser av olika räffeltyper avseende buller visar att detinte finns kända argument för att inte använda sinusräffla, men ytterligare studier kring effekten förförare av tunga fordon rekommenderas. Studien avseende framkomlighetseffekter visar att andelentung trafik är en viktig faktor att beakta i utformningen av mötesfria vägar.
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| 21. |
- Zettergren, Anna, et al.
(author)
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Assessing tobacco use in Swedish young adults from self-report and urinary cotinine : A validation study using the BAMSE birth cohort
- 2023
-
In: BMJ Open. - 2044-6055. ; 13:7
-
Journal article (peer-reviewed)abstract
- Objectives Studies on health effects of tobacco often rely on self-reported exposure data, which is subjective and can lead to misclassification. The aim of this study was to describe the prevalence of cigarette smoking, snus and e-cigarette use, as well as to validate self-reported tobacco use among young adults in Sweden. Method Participants of a population-based Swedish cohort (n=3052), aged 22-25 years, assessed their tobacco use in a web questionnaire. Urinary cotinine was analysed in a subsample of the study population (n=998). The agreement between self-reported tobacco use and urinary cotinine was assessed using Cohen's Kappa coefficient (κ) at a cut-off level of 50 ng/mL. Results Patterns of tobacco use differed between men and women. Among men, 20.0% reported daily snus use, 5.8% daily cigarette smoking and 5.6% any e-cigarette use. In contrast, 3.2% of the women reported daily snus use, 9.0% daily cigarette smoking and 2.4% any e-cigarette use. Among the tobacco use categories, daily snus users had the highest levels of cotinine. Of reported non-tobacco users, 3.5% had cotinine levels above the cut-off, compared with 68.0% among both occasional cigarette smokers and snus users, 67.5% among all e-cigarette users and 94.7% and 97.8% among daily cigarette smokers and snus users, respectively. Agreement between self-reported tobacco use and urinary cotinine was classified as strong for daily use of cigarettes (κ=0.824) and snus (κ=0.861), while moderate to weak for occasional smoking (κ=0.618), occasional snus use (κ=0.573) and any e-cigarette use (κ=0.576). Conclusions We found high validity of self-reported tobacco use in our study population, particularly for daily tobacco use. Further, we found that daily snus users were exposed to high levels of cotinine. Together with previous findings, our results indicate good validity of self-reported tobacco use among young adults.
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| 22. |
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| 23. |
- Ahlford, Marianne, et al.
(author)
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Uppsala Underdogs - A Robot Soccer Project
- 2006
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Reports (pop. science, debate, etc.)abstract
- In this paper, we describe the four-legged soccer team Uppsala Underdogs developed by a group of 4th year computer science students at Uppsala University during the fall of 2004. The project is based on the experience from two similar previous projects. This year the emphasis of the project has been on distribution of data and on support for evaluation and reconfiguration of strategies. To support data distribution, a middleware has been developed, which implements a replication algorithm and provides a clean interface for the other software modules (or behaviors). To enable easy reconfiguration of strategies, an automata-based graphical description language has been developed, which can be compiled into code that uses the database and the lower level modules, such as tactics and positioning, to make decisions and control the robot. In addition, a graphical simulator has been developed in which the strategies can be evaluated.
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| 24. |
- Ahmadi, Zainab, et al.
(author)
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Agreement of the modified Medical Research Council and New York Heart Association scales for assessing the impact of self-rated breathlessness in cardiopulmonary disease
- 2022
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In: ERJ Open Research. - : European Respiratory Society. - 2312-0541. ; 8:1
-
Journal article (peer-reviewed)abstract
- Background: The functional impact of breathlessness is assessed using the modified Medical Research Council (mMRC) scale for chronic respiratory disease and with the New York Heart Association Functional Classification (NYHA) scale for heart failure. We evaluated agreement between the scales and their concurrent validity with other clinically relevant patient-reported outcomes in cardiorespiratory disease.Methods: Outpatients with stable chronic respiratory disease or heart failure were recruited. Agreement between the mMRC and NYHA scales was analysed using Cramér's V and Kendall's tau B tests. Concurrent validity was evaluated using correlations with clinically relevant measures of breathlessness, anxiety, depression, and health-related quality of life. Analyses were conducted for all participants and separately in chronic obstructive pulmonary disease (COPD) and heart failure.Results: In a total of 182 participants with cardiorespiratory disease, the agreement between the mMRC and NYHA scales was moderate (Cramér's V: 0.46; Kendall's tau B: 0.57) with similar results for COPD (Cramér's V: 0.46; Kendall's tau B: 0.66) and heart failure (Cramér's V: 0.46; Kendall's tau B: 0.67). In the total population, the scales correlated in similar ways to other patient-reported outcomes.Conclusion: In outpatients with cardiorespiratory disease, the mMRC and NYHA scales show moderate to strong correlations and similar associations with other patient-reported outcomes. This supports that the scales are comparable when assessing the impact of breathlessness on function and patient-reported outcomes.
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| 25. |
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| 26. |
- Ahmadi, Zainab, et al.
(author)
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Hypo- and hypercapnia predict mortality in oxygen-dependent chronic obstructive pulmonary disease : a population-based prospective study
- 2014
-
In: Respiratory Research. - : BioMed Central. - 1465-9921 .- 1465-993X. ; 15:1, s. 30-
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The prognostic role of the arterial blood gas tension of carbon dioxide (PaCO2) in severe Chronic Obstructive Pulmonary Disease (COPD) remains unknown. The aim of this study was to estimate the association between PaCO2 and mortality in oxygen-dependent COPD. METHODS: National prospective study of patients starting long-term oxygen therapy (LTOT) for COPD in Sweden between October 1, 2005 and June 30, 2009, with all-cause mortality as endpoint. The association between PaCO2 while breathing air, PaCO2 (air), and mortality was estimated using Cox regression adjusted for age, sex, arterial blood gas tension of oxygen (PaO2), World Health Organization performance status, body mass index, comorbidity, and medications. RESULTS: Of 2,249 patients included, 1,129 (50%) died during a median 1.1 years (IQR 0.6-2.0 years) of observation. No patient was lost to follow-up. PaCO2 (air) independently predicted adjusted mortality (p < 0.001). The association with mortality was U-shaped, with the lowest mortality at approximately PaCO2 (air) 6.5 kPa and increased mortality at PaCO2 (air) below 5.0 kPa and above 7.0 kPa. CONCLUSION: In oxygen-dependent COPD, PaCO2 (air) is an independent prognostic factor with a U-shaped association with mortality.
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| 27. |
- Ahmadi, Zainab, et al.
(author)
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Long-Term Oxygen Therapy 24 vs 15 h/day and Mortality in Chronic Obstructive Pulmonary Disease
- 2016
-
In: PLOS ONE. - San Francisco : Public Library of Science. - 1932-6203. ; 11:9
-
Journal article (peer-reviewed)abstract
- Long-term oxygen therapy (LTOT) ≥ 15 h/day improves survival in hypoxemic chronic obstructive pulmonary disease (COPD). LTOT 24 h/day is often recommended but may pose an unnecessary burden with no clear survival benefit compared with LTOT 15 h/day. The aim was to test the hypothesis that LTOT 24 h/day decreases all-cause, respiratory, and cardiovascular mortality compared to LTOT 15 h/day in hypoxemic COPD. This was a prospective, observational, population-based study of COPD patients starting LTOT between October 1, 2005 and June 30, 2009 in Sweden. Overall and cause-specific mortality was analyzed using Cox and Fine-Gray regression, controlling for age, sex, prescribed oxygen dose, PaO2 (air), PaCO2 (air), Forced Expiratory Volume in one second (FEV1), WHO performance status, body mass index, comorbidity, and oral glucocorticoids. A total of 2,249 included patients were included with a median follow-up of 1.1 years (interquartile range, 0.6-2.1). 1,129 (50%) patients died and no patient was lost to follow-up. Higher LTOT duration analyzed as a continuous variable was not associated with any change in mortality rate (hazard ratio [HR] 1.00; (95% confidence interval [CI], 0.98 to 1.02) per 1 h/day increase above 15 h/day. LTOT exactly 24 h/day was prescribed in 539 (24%) patients and LTOT 15-16 h/day in 1,231 (55%) patients. Mortality was similar between the groups for all-cause, respiratory and cardiovascular mortality. In hypoxemic COPD, LTOT 24 h/day was not associated with a survival benefit compared with treatment 15-16 h/day. A design for a registry-based randomized trial (R-RCT) is proposed.
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| 28. |
- Albrektson, Anna, 1966-, et al.
(author)
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Cool Nature : Utopian Landscapes in Sweden 1780–1840
- 2022
-
In: Sjuttonhundratal. - : UiT The Arctic University of Norway. - 1652-4772 .- 2001-9866. ; 19, s. 94-116
-
Journal article (peer-reviewed)abstract
- In this essay, an interdisciplinary group of researchers sets out to address the period 1780–1840 in Sweden in a new way, by placing nature at its centre. With the help of ecocritical and transcultural theory, combined with renewed attention to the Swedish fine arts, learned discourses, and practices, we suggest a new approach to these revolutionary decades. The perceived dissonance, the interplay between climatic conditions and cultural template in early modern and modern Sweden, has not been fully addressed in current research, despite the fact that the relationship between humankind and the environment is a central issue in contemporary society and scholarship. Representations of nature situate the nation, they negotiate the relationship between a sensed reality and an ideal, between human and more-than-human beings. We suggest a focus on the unpredictable space created by negotiations of nature in Swedish representations during this crucial period, and, furthermore, on the ways in which this creative space is charged with utopian possibilities in the early Anthropocene. This is the background and the driving force of the planned research project ‘Cool Nature: Utopian Landscapes in Sweden 1780–1840’.
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| 29. |
- Alfvén, Tobias, et al.
(author)
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Mpox hos barn – svenskt perspektiv : Mpox and children - a Swedish perspective
- 2023
-
In: Läkartidningen. - 0023-7205. ; 120
-
Journal article (other academic/artistic)abstract
- Mpox (monkeypox) is an infection caused by the monkeypox virus, which belongs to the same family as the smallpox virus. Sporadic infections in humans have been known since the 1970s. Since spring 2022 there has been a global epidemic. The large majority of the mpox cases in the ongoing epidemic have been reported in adult men, the number of infected children is small. The typical manifestation of mpox includes a rash that initially presents as maculopapular lesions and then develops into vesicles and eventually crusts. Transmission of the virus primarily occurs through close contact with infected individuals, particularly through contact with unhealed blisters or wounds, as well as through sexual contacts and exposure to body fluids. In cases of documented close contact with an infected individual, post-exposure prophylaxis is recommended and may also be administered to children whose guardians have contracted mpox.
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| 30. |
- Allgardsson, Anders, et al.
(author)
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An unusual dimeric inhibitor of acetylcholinesterase : cooperative binding of crystal violet
- 2017
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In: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 22:9
-
Journal article (peer-reviewed)abstract
- Acetylcholinesterase (AChE) is an essential enzyme that terminates cholinergic transmission by a rapid hydrolysis of the neurotransmitter acetylcholine. AChE is an important target for treatment of various cholinergic deficiencies, including Alzheimer's disease and myasthenia gravis. In a previous high throughput screening campaign, we identified the dye crystal violet (CV) as an inhibitor of AChE. Herein, we show that CV displays a significant cooperativity for binding to AChE, and the molecular basis for this observation has been investigated by X-ray crystallography. Two monomers of CV bind to residues at the entrance of the active site gorge of the enzyme. Notably, the two CV molecules have extensive intermolecular contacts with each other and with AChE. Computational analyses show that the observed CV dimer is not stable in solution, suggesting the sequential binding of two monomers. Guided by the structural analysis, we designed a set of single site substitutions, and investigated their effect on the binding of CV. Only moderate effects on the binding and the cooperativity were observed, suggesting a robustness in the interaction between CV and AChE. Taken together, we propose that the dimeric cooperative binding is due to a rare combination of chemical and structural properties of both CV and the AChE molecule itself.
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| 31. |
- Allgardsson, Anders, et al.
(author)
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Structure of a prereaction complex between the nerve agent sarin, its biological target acetylcholinesterase, and the antidote HI-6
- 2016
-
In: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 113:20, s. 5514-5519
-
Journal article (peer-reviewed)abstract
- Organophosphorus nerve agents interfere with cholinergic signaling by covalently binding to the active site of the enzyme acetylcholinesterase (AChE). This inhibition causes an accumulation of the neurotransmitter acetylcholine, potentially leading to overstimulation of the nervous system and death. Current treatments include the use of antidotes that promote the release of functional AChE by an unknown reactivation mechanism. We have used diffusion trap cryocrystallography and density functional theory (DFT) calculations to determine and analyze prereaction conformers of the nerve agent antidote HI-6 in complex with Mus musculus AChE covalently inhibited by the nerve agent sarin. These analyses reveal previously unknown conformations of the system and suggest that the cleavage of the covalent enzyme-sarin bond is preceded by a conformational change in the sarin adduct itself. Together with data from the reactivation kinetics, this alternate conformation suggests a key interaction between Glu202 and the O-isopropyl moiety of sarin. Moreover, solvent kinetic isotope effect experiments using deuterium oxide reveal that the reactivation mechanism features an isotope-sensitive step. These findings provide insights into the reactivation mechanism and provide a starting point for the development of improved antidotes. The work also illustrates how DFT calculations can guide the interpretation, analysis, and validation of crystallographic data for challenging reactive systems with complex conformational dynamics.
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| 32. |
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| 33. |
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| 34. |
- Andersson, C. David, et al.
(author)
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Benefits of statistical molecular design, covariance analysis, and reference models in QSAR : a case study on acetylcholinesterase
- 2015
-
In: Journal of Computer-Aided Molecular Design. - : Springer Science and Business Media LLC. - 0920-654X .- 1573-4951. ; 29:3, s. 199-215
-
Journal article (peer-reviewed)abstract
- Scientific disciplines such as medicinal- and environmental chemistry, pharmacology, and toxicology deal with the questions related to the effects small organic compounds exhort on biological targets and the compounds' physicochemical properties responsible for these effects. A common strategy in this endeavor is to establish structure-activity relationships (SARs). The aim of this work was to illustrate benefits of performing a statistical molecular design (SMD) and proper statistical analysis of the molecules' properties before SAR and quantitative structure-activity relationship (QSAR) analysis. Our SMD followed by synthesis yielded a set of inhibitors of the enzyme acetylcholinesterase (AChE) that had very few inherent dependencies between the substructures in the molecules. If such dependencies exist, they cause severe errors in SAR interpretation and predictions by QSAR-models, and leave a set of molecules less suitable for future decision-making. In our study, SAR- and QSAR models could show which molecular sub-structures and physicochemical features that were advantageous for the AChE inhibition. Finally, the QSAR model was used for the prediction of the inhibition of AChE by an external prediction set of molecules. The accuracy of these predictions was asserted by statistical significance tests and by comparisons to simple but relevant reference models.
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| 35. |
- Andersson, C. David, et al.
(author)
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Divergent Structure-Activity Relationships of Structurally Similar Acetylcholinesterase Inhibitors
- 2013
-
In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 56:19, s. 7615-7624
-
Journal article (peer-reviewed)abstract
- The molecular interactions between the enzyme acetylcholinesterase (AChE) and two compound classes consisting of N-[2-(diethylamino)ethyl]benzenesulfonamides and N-[2-(diethylamino)ethyl]benzenemethanesulfonamides have been investigated using organic synthesis, enzymatic assays, X-ray crystallography, and thermodynamic profiling. The inhibitors' aromatic properties were varied to establish structure activity relationships (SAR) between the inhibitors and the peripheral anionic site (PAS) of AChE. The two structurally similar compound classes proved to have distinctly divergent SARs in terms of their inhibition capacity of AChE. Eight X-ray structures revealed that the two sets have different conformations in PAS. Furthermore, thermodynamic profiles of the binding between compounds and AChE revealed class-dependent differences of the entropy/enthalpy contributions to the free energy of binding. Further development of the entropy-favored compound class resulted in the synthesis of the most potent inhibitor and an extension beyond the established SARs. The divergent SARs will be utilized to develop reversible inhibitors of AChE into reactivators of nerve agent-inhibited AChE.
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| 36. |
- Andersson, C. David, 1978-, et al.
(author)
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Influence of Enantiomeric Inhibitors on the Dynamics of Acetylcholinesterase Measured by Elastic Incoherent Neutron Scattering
- 2018
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In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 122:36, s. 8516-8525
-
Journal article (peer-reviewed)abstract
- The enzyme acetylcholinesterase (AChE) is essential in humans and animals because it catalyzes the breakdown of the nerve-signaling substance acetylcholine. Small molecules that inhibit the function of AChE are important for their use as drugs in the, for example, symptomatic treatment of Alzheimer's disease. New and improved inhibitors are warranted, mainly because of severe side effects of current drugs. In the present study, we have investigated if and how two enantiomeric inhibitors of AChE influence the overall dynamics of noncovalent complexes, using elastic incoherent neutron scattering. A fruitful combination of univariate models, including a newly developed non-Gaussian model for atomic fluctuations, and multivariate methods (principal component analysis and discriminant analysis) was crucial to analyze the fine details of the data. The study revealed a small but clear increase in the dynamics of the inhibited enzyme compared to that of the noninhibited enzyme and contributed to the fundamental knowledge of the mechanisms of AChE-inhibitor binding valuable for the future development of inhibitors.
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| 37. |
- Andersson, C. David, 1978-, et al.
(author)
-
Physical Mechanisms Governing Substituent Effects on Arene-Arene Interactions in a Protein Milieu
- 2020
-
In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 124:30, s. 6529-6539
-
Journal article (peer-reviewed)abstract
- Arene-arene interactions play important roles in protein-ligand complex formation. Here, we investigate the characteristics of arene-arene interactions between small organic molecules and aromatic amino acids in protein interiors. The study is based on X-ray crystallographic data and quantum mechanical calculations using the enzyme acetylcholinesterase and selected inhibitory ligands as a model system. It is shown that the arene substituents of the inhibitors dictate the strength of the interaction and the geometry of the resulting complexes. Importantly, the calculated interaction energies correlate well with the measured inhibitor potency. Non-hydrogen substituents strengthened all interaction types in the protein milieu, in keeping with results for benzene dimer model systems. The interaction energies were dispersion-dominated, but substituents that induced local dipole moments increased the electrostatic contribution and thus yielded more strongly bound complexes. These findings provide fundamental insights into the physical mechanisms governing arene-arene interactions in the protein milieu and thus into molecular recognition between proteins and small molecules.
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| 38. |
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| 39. |
- Artursson, Elisabet, et al.
(author)
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Catalytic-site conformational equilibrium in nerve-agent adducts of acetylcholinesterase : Possible implications for the HI-6 antidote substrate specificity
- 2013
-
In: Biochemical Pharmacology. - : Elsevier. - 0006-2952 .- 1356-1839. ; 85:9, s. 1389-1397
-
Journal article (peer-reviewed)abstract
- Nerve agents such as tabun, cyclosarin and Russian VX inhibit the essential enzyme acetylcholinesterase (AChE) by organophosphorylating the catalytic serine residue. Nucleophiles, such as oximes, are used as antidotes as they can reactivate and restore the function of the inhibited enzyme. The oxime HI-6 shows a notably low activity on tabun adducts but can effectively reactivate adducts of cyclosarin and Russian VX. To examine the structural basis for the pronounced substrate specificity of HI-6, we determined the binary crystal structures of Mus musculus AChE (mAChE) conjugated by cyclosarin and Russian VX and found a conformational mobility of the side chains of Phe338 and His447. The interaction between HI-6 and tabun-adducts of AChE were subsequently investigated using a combination of time resolved fluorescence spectroscopy and X-ray crystallography. Our findings show that HI-6 binds to tabun inhibited Homo sapiens AChE (hAChE) with an IC50 value of 300 μM and suggest that the reactive nucleophilic moiety of HI-6 is excluded from the phosphorus atom of tabun. We propose that a conformational mobility of the side-chains of Phe338 and His447 is a common feature in nerve-agent adducts of AChE. We also suggest that the conformational mobility allow HI-6 to reactivate conjugates of cyclosarin and Russian VX while a reduced mobility in tabun conjugated AChE results in steric hindrance that prevents efficient reactivation.
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| 40. |
- Arvidsson, Anna K, 1971-, et al.
(author)
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Friktions- och texturutveckling på nya beläggningar
- 2019
-
Reports (other academic/artistic)abstract
- En ny vägyta bör vara och upplevas som säker av trafikanterna oavsett vilket väglag som råder. Det är därför viktigt att vägbanan har en tillfredställande nivå på friktion redan när vägen öppnas. Det finns begränsade dokumenterade kunskaper hur vägen förändras den första tiden efter en beläggningsåtgärd.Syftet med detta projekt är att fastställa hur friktionen förändras under den första tiden efter att vägbeläggningen är lagd och trafikpåsläpp sker. Ambitionen är att kunna avgöra om nylagda vägavsnitt har nedsatt friktion och ge rekommendationer för när en friktionsmätning ska utföras och hur skyltning ska ske i anslutning till beläggningsarbeten. Upplägget har varit att följa olika objekt med täta friktions- och texturmätningar från strax innan trafikpåsläpp tills nivåerna har stabiliserats.Initialt är friktionen hög för att sen avta med mängden trafik. Efter 1–3 veckor nåddes det lägsta värdet och därefter ökade eller stabiliserades friktionen. Gemensamt för alla undersökta sträckor var att det sker stora förändringar i texturnivåerna från att det första fordonet trafikerar vägen och därefter är den starkaste tendensen en sjunkande texturnivå tills en stabil nivå uppnås efter 1–3 veckor.
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| 41. |
- Astell, A. J., et al.
(author)
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Developing a pragmatic evaluation of ICTs for older adults with cognitive impairment at scale : the IN LIFE experience
- 2022
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In: Universal Access in the Information Society. - Heidelberg, Germany : Springer. - 1615-5289 .- 1615-5297. ; 21:1, s. 1-19
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Journal article (peer-reviewed)abstract
- Implementing information and communications technology (ICT) at scale requires evaluation processes to capture the impacton users as well as the infrastructure into which it is being introduced. For older adults living with cognitive impairment, thisrequires evaluation that can accommodate diferent levels of cognitive impairment, alongside input from family and formalcaregivers, plus stakeholder organisations. The European Horizon 2020 project INdependent LIving support Functions forthe Elderly (IN LIFE) set out to integrate 17 technologies into a single digital platform for older people living with cognitive impairment plus their families, care providers and stakeholders. The IN LIFE evaluation took place across six nationalpilot sites to examine a number of variables including impact on the users, user acceptance of the individual services andthe overall platform, plus the economic case for the IN LIFE platform. The results confrmed the interest and need amongolder adults, family caregivers, formal caregivers and stakeholders, for information and communications technology (ICT).Relative to the baseline, quality of life improved and cognition stabilised; however, there was an overall reluctance to payfor the platform. The fndings provide insights into existing barriers and challenges for adoption of ICT for older peopleliving with cognitive impairment.
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| 42. |
- Berg, Lotta, 1985-
(author)
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Exploring non-covalent interactions between drug-like molecules and the protein acetylcholinesterase
- 2017
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Doctoral thesis (other academic/artistic)abstract
- The majority of drugs are small organic molecules, so-called ligands, that influence biochemical processes by interacting with proteins. The understanding of how and why they interact and form complexes is therefore a key component for elucidating the mechanism of action of drugs. The research presented in this thesis is based on studies of acetylcholinesterase (AChE). AChE is an essential enzyme with the important function of terminating neurotransmission at cholinergic synapses. AChE is also the target of a range of biologically active molecules including drugs, pesticides, and poisons. Due to the molecular and the functional characteristics of the enzyme, it offers both challenges and possibilities for investigating protein-ligand interactions. In the thesis, complexes between AChE and drug-like ligands have been studied in detail by a combination of experimental techniques and theoretical methods. The studies provided insight into the non-covalent interactions formed between AChE and ligands, where non-classical CH∙∙∙Y hydrogen bonds (Y = O or arene) were found to be common and important. The non-classical hydrogen bonds were characterized by density functional theory calculations that revealed features that may provide unexplored possibilities in for example structure-based design. Moreover, the study of two enantiomeric inhibitors of AChE provided important insight into the structural basis of enthalpy-entropy compensation. As part of the research, available computational methods have been evaluated and new approaches have been developed. This resulted in a methodology that allowed detailed analysis of the AChE-ligand complexes. Moreover, the methodology also proved to be a useful tool in the refinement of X-ray crystallographic data. This was demonstrated by the determination of a prereaction conformation of the complex between the nerve-agent antidote HI-6 and AChE inhibited by the nerve agent sarin. The structure of the ternary complex constitutes an important contribution of relevance for the design of new and improved drugs for treatment of nerve-agent poisoning. The research presented in the thesis has contributed to the knowledge of AChE and also has implications for drug discovery and the understanding of biochemical processes in general.
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| 43. |
- Berg, Lotta, et al.
(author)
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Similar but Different : Thermodynamic and Structural Characterization of a Pair of Enantiomers Binding to Acetylcholinesterase
- 2012
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In: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 51:51, s. 12716-12720
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Journal article (peer-reviewed)abstract
- Take a closer look: Unexpectedly, a pair of enantiomeric ligands proved to have similar binding affinities for acetylcholinesterase. Further studies indicated that the enantiomers exhibit different thermodynamic profiles. Analyses of the noncovalent interactions in the protein-ligand complexes revealed that these differences are partly due to nonclassical hydrogen bonds between the ligands and aromatic side chains of the protein.
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| 44. |
- Berg, Lotta, et al.
(author)
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The Nature of Activated Non-classical Hydrogen Bonds : A Case Study on Acetylcholinesterase-Ligand Complexes
- 2016
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In: Chemistry - A European Journal. - : Wiley-VCH Verlagsgesellschaft. - 0947-6539 .- 1521-3765. ; 22:8, s. 2672-2681
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Journal article (peer-reviewed)abstract
- Molecular recognition events in biological systems are driven by non-covalent interactions between interacting species. Here, we have studied hydrogen bonds of the CHY type involving electron-deficient CH donors using dispersion-corrected density functional theory (DFT) calculations applied to acetylcholinesterase-ligand complexes. The strengths of CHY interactions activated by a proximal cation were considerably strong; comparable to or greater than those of classical hydrogen bonds. Significant differences in the energetic components compared to classical hydrogen bonds and non-activated CHY interactions were observed. Comparison between DFT and molecular mechanics calculations showed that common force fields could not reproduce the interaction energy values of the studied hydrogen bonds. The presented results highlight the importance of considering CHY interactions when analysing protein-ligand complexes, call for a review of current force fields, and opens up possibilities for the development of improved design tools for drug discovery.
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| 45. |
- Bergh, Ingrid H. E., et al.
(author)
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Assessment and documentation of women's labour pain : A cross-sectional study in Swedish delivery wards
- 2015
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In: Women and Birth. - : Elsevier. - 1871-5192 .- 1878-1799. ; 28:2, s. E14-E18
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Journal article (peer-reviewed)abstract
- Background: A woman's pain during labour plays a dominant role in childbirth. The midwife's role is to assess the degree of pain experienced during labour. When professionals respond to labour pain with acknowledgement and understanding, the woman's sense of control and empowerment is increased, which could contribute to a positive experience of childbirth. The aim of this study is to describe how labour pain in Swedish delivery wards is assessed and documented. Methods: This quantitative descriptive study was designed as a national survey performed through telephone interviews with the representatives of 34 delivery wards in Sweden. Results and conclusion: The majority of the participating delivery wards assessed and documented women's labour pain, but in an unstructured manner. The wards differed in how the assessments and documentation were performed. In addition, almost all the delivery wards that participated in the survey lacked guidelines for the assessment and documentation of the degree of pain during labour. The findings also showed that the issue of labour pain was sometimes discussed in the delivery wards, but not in a structured or consistent way. (C) 2015 Australian College of Midwives. Published by Elsevier Australia (a division of Reed International Books Australia Pty Ltd). All rights reserved.
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| 46. |
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| 47. |
- Björkander, Sophia, et al.
(author)
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SARS-CoV-2-specific B- and T-cell immunity in a population-based study of young Swedish adults
- 2022
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In: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 149:1, s. 65-75
-
Journal article (peer-reviewed)abstract
- Background: Young adults are now considered major spreaders of coronavirus disease 2019 (COVID-19) disease. Although most young individuals experience mild to moderate disease, there are concerns of long-term adverse health effects. The impact of COVID-19 disease and to which extent population-level immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exists in young adults remain unclear.Objective: We conducted a population-based study on humoral and cellular immunity to SARS-CoV-2 and explored COVID-19 disease characteristics in young adults.Methods: We invited participants from the Swedish BAMSE (Barn [Children], Allergy Milieu, Stockholm, Epidemiology) birth cohort (age 24-27 years) to take part in a COVID-19 followup. From 980 participants (October 2020 to June 2021), we here present data on SARS-CoV-2 receptor-binding domain-specific IgM, IgA, and IgG titers measured by ELISA and on symptoms and epidemiologic factors associated with seropositivity. Further, SARS-CoV-2-specific memory B-and T-cell responses were detected for a subpopulation (n 5 108) by ELISpot and FluoroSpot.Results: A total of 28.4% of subjects were seropositive, of whom 18.4% were IgM single positive. One in 7 seropositive subjects was asymptomatic. Seropositivity was associated with use of public transport, but not with sex, asthma, rhinitis, IgE sensitization, smoking, or body mass index. In a subset of representative samples, 20.7% and 35.0% had detectable SARSCoV-2 specific B-and T-cell responses, respectively. B-and T-cell memory responses were clearly associated with seropositivity, but T-cell responses were also detected in 17.2% of seronegative subjects.Conclusions: Assessment of IgM and T-cell responses may improve population-based estimations of SARS-CoV-2 infection. The pronounced surge of both symptomatic and asymptomatic infections among young adults indicates that the large-scale vaccination campaign should be continued. (J Allergy Clin Immunol 2022;149:65-75.)
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| 48. |
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| 49. |
- Blomberg, Anders, et al.
(author)
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Chronic Airflow Limitation, Emphysema and Impaired Diffusing Capacity in Relation to Smoking Habits in a Swedish Middle-Aged Population.
- 2024
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In: Annals of the American Thoracic Society. - 2329-6933 .- 2325-6621.
-
Journal article (peer-reviewed)abstract
- RATIONALE: Chronic obstructive pulmonary disease (COPD) includes respiratory symptoms and chronic airflow limitation (CAL). In some cases, emphysema and impaired diffusing capacity for carbon monoxide (DLCO) are present, but characteristics and symptoms vary with smoking exposure.OBJECTIVES: To study the prevalence of CAL, emphysema and impaired DLCO in relation to smoking and respiratory symptoms in a middle-aged population.METHODS: We investigated 28,746 randomly invited individuals (52% women) aged 50-64 years across six Swedish sites. We performed spirometry, DLCO, high-resolution computed tomography (HRCT) and asked for smoking habits and respiratory symptoms. CAL was defined as post-bronchodilator forced expiratory volume in 1 second divided by forced expiratory volume (FEV1/FVC)<0.7.RESULTS: The overall prevalence was for CAL 8.8%, for impaired DLCO (DLCOCONCLUSIONS: In this large population-based study of middle-aged people, CAL and impaired DLCO were associated with common respiratory symptoms. Self-reported asthma was not associated with CAL in never-smokers. Our findings suggest that CAL in never-smokers signifies a separate clinical phenotype that may be monitored and, possibly, treated differently from smoking-related COPD. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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| 50. |
- Blomqvist, Else-Gun, et al.
(author)
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Intervju med Ingrid Gunter, f.d. bibliotekarie vid Jonsereds bibliotek
- 1976
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Other publication (pop. science, debate, etc.)abstract
- Interview with Ingrid Gunter, born in 1920. She was a public librarian in Jonsered. The interview was conducted by Else-Gun Blomqvist, Per Dessborn, Margareta Ekström, Anna-Lena Holm, Britt Håkansson and Charlotte Åslin, students of the Swedish School of Library and Information Science in Borås, in 1976.
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