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1.
  • Rydberg Sterner, Therese, et al. (författare)
  • Depression in relation to sex and gender expression among Swedish septuagenarians-Results from the H70 study
  • 2020
  • Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 15:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Little is known about the role of gender expression (femininity, masculinity, or androgyny) in relation to sex differences in depression. This study tested if gender expression was associated with depression and burden of depressive symptoms in a 70-year-old population. Methods A cross-sectional population-based sample of 70-year-olds from The Gothenburg H70 Birth Cohort Study (n = 1203) was examined in 2014-16. Data were collected using psychiatric examinations and structured questionnaires, including the Positive-Negative Sex-Role Inventory to assess gender expression. Depression was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders criteria, and symptom burden was assessed with Montgomery angstrom sberg Depression Rating Scale (MADRS). Results Gender expression was related to MADRS score and depression diagnosis. In fully adjusted models, feminine traits with low social desirability (FEM-) were associated with a higher MADRS score (R(2)0.16; B 0.16; CI 0.1-0.2), while androgyny (t ratio) (R(2)0.12; B 0.42; CI 0.1-0.7) and masculine traits with high social desirability (MAS+) (R(2)0.13; B -0.06; CI -0.1--0.01) were associated with a lower MADRS score. Also, feminine traits with low social desirability (FEM-) were positively associated with depression (OR 1.04; CI 1.01-1.1). No associations between depression and masculinity or androgyny were observed in adjusted models. There were no interactions between sex and gender expression in relation to depression or MADRS score, indicating that the effects of gender expression were similar in men and women. Conclusions We found that gender expression was associated to both depression and burden of depressive symptoms. More specifically, we found that femininity was associated to higher levels of depression, irrespective of biological sex. In addition, masculinity and androgyny were associated with lower levels of depression. These results highlight the importance of taking gender expression into consideration when studying sex differences in depression among older populations in future studies.
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2.
  • Rydberg Sterner, Therese, et al. (författare)
  • The Gothenburg H70 Birth cohort study 2014-16: design, methods and study population.
  • 2019
  • Ingår i: European journal of epidemiology. - : Springer Science and Business Media LLC. - 1573-7284 .- 0393-2990. ; 34:2, s. 191-209
  • Tidskriftsartikel (refereegranskat)abstract
    • To improve health care for older persons, we need to learn more about ageing, e.g. identify protective factors and early markers for diseases. The Gothenburg H70 Birth Cohort Studies (the H70 studies) are multidisciplinary epidemiological studies examining representative birth cohorts of older populations in Gothenburg, Sweden. So far, six birth cohorts of 70-year-olds have been examined over time, and examinations have been virtually identical between studies. This paper describes the study procedures for the baseline examination of the Birth cohort 1944, conducted in 2014-16. In this study, all men and women born 1944 on specific dates, and registered as residents in Gothenburg, were eligible for participation (n=1839). A total of 1203 (response rate 72.2%; 559 men and 644 women; mean age 70.5years) agreed to participate in the study. The study comprised sampling of blood and cerebrospinal fluid, psychiatric, cognitive, and physical health examinations, examinations of genetics and family history, use of medications, social factors, functional ability and disability, physical fitness and activity, body composition, lung function, audiological and ophthalmological examinations, diet, brain imaging, as well as a close informant interview, and qualitative studies. As in previous examinations, data collection serves as a basis for future longitudinal follow-up examinations. The research gained from the H70 studies has clinical relevance in relation to prevention, early diagnosis, clinical course, experience of illness, understanding pathogenesis and prognosis. Results will increase our understanding of ageing and inform service development, which may lead to enhanced quality of care for older persons.
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3.
  • Rydén, Lina, 1982, et al. (författare)
  • Attrition in the Gothenburg H70 birth cohort studies, an 18-year follow-up of the 1930 cohort
  • 2023
  • Ingår i: Frontiers in Epidemiology. - 2674-1199. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Longitudinal studies are essential to understand the ageing process, and risk factors and consequences for disorders, but attrition may cause selection bias and impact generalizability. We describe the 1930 cohort of the Gothenburg H70 Birth Cohort Studies, followed from age 70 to 88, and compare baseline characteristics for those who continue participation with those who die, refuse, and drop out for any reason during follow-up. Methods: A population-based sample born 1930 was examined with comprehensive assessments at age 70 (N = 524). The sample was followed up and extended to increase sample size at age 75 (N = 767). Subsequent follow-ups were conducted at ages 79, 85, and 88. Logistic regression was used to analyze baseline characteristics in relation to participation status at follow-up. Results: Refusal to participate in subsequent examinations was related to lower educational level, higher blood pressure, and lower scores on cognitive tests. Both attrition due to death and total attrition were associated with male sex, lower educational level, smoking, ADL dependency, several diseases, poorer lung function, slower gait speed, lower scores on cognitive tests, depressive symptoms, and a larger number of medications. Attrition due to death was also associated with not having a partner. Conclusions: It is important to consider different types of attrition when interpreting results from longitudinal studies, as representativeness and results may be differently affected by different types of attrition. Besides reducing barriers to participation, methods such as imputation and weighted analyses can be used to handle selection bias.
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4.
  • Wetterberg, Hanna, et al. (författare)
  • Representativeness in population-based studies of older adults: five waves of cross-sectional examinations in the Gothenburg H70 Birth Cohort Study
  • 2022
  • Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 12:12
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectivesTo describe representativeness in the Gothenburg H70 1930 Birth Cohort Study.DesignRepeated cross-sectional examinations of a population-based study.SettingGothenburg, Sweden.ParticipantsAll residents of Gothenburg, Sweden, born on specific birth dates in 1930 were invited to a comprehensive health examination at ages 70, 75, 79, 85 and 88. The number of participants at each examination was 524 at age 70, 767 at age 75, 580 at age 79, 416 at age 85, and 258 at age 88.Primary outcome measuresWe compared register data on sociodemographic characteristics and hospital discharge diagnoses between participants and (1) refusals, (2) all same-aged individuals in Gothenburg and (3) all same-aged individuals in Sweden. We also compared mortality rates between participants and refusals.ResultsRefusal rate increased with age. At two or more examination waves, participants compared with refusals had higher educational level, more often had osteoarthritis, had lower mortality rates, had lower prevalence of neuropsychiatric, alcohol-related and cardiovascular disorders, and were more often married. At two examination waves, participants compared with same-aged individuals in Gothenburg had higher education and were more often born in Sweden. At two examination waves or more, participants compared with same-aged individuals in Sweden had higher education, had higher average income, less often had ischaemic heart disease, were less often born in Sweden and were more often divorced.ConclusionsParticipants were more similar to the target population in Gothenburg than to refusals and same-aged individuals in Sweden. Our study shows the importance of having different comparison groups when assessing representativeness of population studies, which is important in evaluating generalisability of results. The study also contributes unique and up-to-date knowledge about participation bias in these high age groups.
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5.
  • Jonson, Mattias, et al. (författare)
  • Passive and active suicidal ideation in Swedish 85-year-olds: Time trends 1986-2015
  • 2021
  • Ingår i: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 290, s. 300-307
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract Background Older adults have high suicide rates. We investigated potential time trends in the prevalence of passive and active suicidal ideation in 85-year-olds. Further, we examined factors associated with such ideation in this age group. Methods Population-based samples of 85-year-olds were interviewed in 1986 (N=347), 2008 (N=426) and 2015 (N=320). Past-month passive/active suicidal ideation was evaluated with the Paykel questions. Results Reporting any type of passive or active suicidal ideation was less common in 2008 (7.3%, p<0.001) and 2015 (7.2%, p<0.001) compared to 1986 (16.4%). The change was driven by decreases in passive ideation. Passive/active suicidal ideation was associated with higher MADRS score (OR: 1.2, 95% CI: 1.1-1.2, p<0.001), institution residence (OR: 3.9, 95% CI: 1.7-8.9, p=0.001) and feelings of loneliness (OR: 2.7, 95% CI: 1.4-5.2, p=0.003). When stratified by sex, it was associated with institution residence (OR: 3.7, 95% CI: 1.4-9.9, p=0.008) and feelings of loneliness (OR: 3.0, 95% CI: 1.4-6.3, p=0.005) in women. In men, we observed a tenfold higher risk in those without partners (OR: 9.8, 95% CI: 2.9-33.5, p<0.001). Limitations While differential three-year mortality was not observed in 1986, mortality was higher among non-participants in 2008 and 2015. This might have inflated cohort differences in passive/active suicidal ideation. Conclusion An initial decrease in the prevalence of passive/active suicidal ideation in 85-year-olds was observed but this positive trend did not persist. Results underline that preventive strategies targeting loneliness and focusing on institutional settings are needed, as are interventions for men without partners.
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6.
  • Jonson, Mattias, et al. (författare)
  • Time trends in depression prevalence among Swedish 85-year-olds: Repeated cross-sectional population-based studies in 1986, 2008, and 2015
  • 2023
  • Ingår i: Psychological Medicine. - 0033-2917 .- 1469-8978. ; 53:6, s. 2456-2465
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Octogenarians of today are better educated, and physically and cognitively healthier, than earlier born cohorts. Less is known about time trends in mental health in this age group. We aimed to study time trends in the prevalence of depression and psychotropic drug use among Swedish 85-year-olds. Methods We derived data from interviews with 85-year-olds in 1986-1987 (N = 348), 2008-2010 (N = 433) and 2015-17 (N = 321). Depression diagnoses were made according to the Diagnostic and Statistical Manual of Mental Disorders. Symptom burden was assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS). Information on psychotropic drug use, sociodemographic, and health-related factors were collected during the interviews. Results The prevalence of major depression was lower in 2015-2017 (4.7%, p < 0.001) and 2008-2010 (6.9%, p = 0.010) compared to 1986-1987 (12.4%). The prevalence of minor depression was lower in 2015-2017 (8.1%) compared to 2008-2010 (16.2%, p = 0.001) and 1986-1987 (17.8%, p < 0.001). Mean MADRS score decreased from 8.0 in 1986-1987 to 6.5 in 2008-2010, and 5.1 in 2015-2017 (p < 0.001). The reduced prevalence of depression was not explained by changes in sociodemographic and health-related risk factors for depression. While psychoactive drug use was observed in a third of the participants in each cohort, drug type changed over time (increased use of antidepressants and decreased use of anxiolytics and antipsychotics). Conclusions The prevalence of depression in octogenarians has declined during the past decades. The decline was not explained by changes in known risk factors for depression. The present study cannot answer whether changed prescription patterns of psychoactive drugs have contributed to the decline.
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7.
  • Mellqvist Fässberg, Madeleine, et al. (författare)
  • Epidemiology of suicidal feelings in an ageing Swedish population: From old to very old age in the Gothenburg H70 Birth Cohort Studies
  • 2020
  • Ingår i: Epidemiology and Psychiatric Sciences. - 2045-7960. ; 29
  • Tidskriftsartikel (refereegranskat)abstract
    • AimsThe first aim of this study was to provide prevalence suicidal feelings over time (past week, past month, past year and lifetime) in a population-based sample of old to very old adults without dementia. Does prevalence change with rising age? The second aim was to examine the fluctuation of suicidal feelings over time. How does this coincide with depression status?MethodsData were derived from the Gothenburg H70 Birth Cohort Studies (the H70 studies) which are multidisciplinary longitudinal studies on ageing. A representative sample of adults in Gothenburg, Sweden with birth years 1901-1944 were invited to take part in a longitudinal health study on ageing and participated at one or more occasions during 1986-2014. The sample consisted of 6668 observations originating from 3972 participants without dementia between the ages of 70 and 108, including 1604 participants with multiple examination times. Suicidal feelings were examined during a psychiatric interview using the Paykel questions (life not worth living, death wishes, thoughts of taking own life, seriously considered taking life, attempted suicide).ResultsPrevalence figures for suicidal feelings of any severity were as follows: past week 4.8%, past month 6.7%, past year 11.2% and lifetime 25.2%. Prevalence rates increased with age in the total group and in women but not in men. Suicidal feelings were common in participants with concurrent major or minor depression, but over a third of the participants who reported suicidal feelings did not fulfil criteria for these diagnoses nor did they present elevated mean depressive symptom scores. The majority of participants consistently reported no experience of suicidal feelings over multiple examination times, but fluctuation was more common in women compared with men.ConclusionSuicidal feelings in late-life are uncommon in individuals without depression indicating that such behaviour is not a widespread, normative phenomenon. However, such feelings may occur outside the context of depression. © Cambridge University Press 2019.
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8.
  • Wallengren, Ola, et al. (författare)
  • Comparison of the 2010 and 2019 diagnostic criteria for sarcopenia by the European Working Group on Sarcopenia in Older People (EWGSOP) in two cohorts of Swedish older adults.
  • 2021
  • Ingår i: BMC geriatrics. - : Springer Science and Business Media LLC. - 1471-2318. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The operational definition of sarcopenia has been updated (EWGSOP2) and apply different cut-off points compared to previous criteria (EWGSOP1). Therefore, we aim to compare the sarcopenia prevalence and the association with mortality and dependence in activities of daily living using the 2010 (EWGSOP1 and 2019 (EWGSOP2 operational definition, applying cut-offs at two levels using T-scores.Two birth cohorts, 70 and 85-years-old (n=884 and n=157, respectively), were assessed cross-sectionally (57% women). Low grip strength, low muscle mass and slow gait speed were defined below -2.0 and-2.5 SD from a young reference population (T-score). Muscle mass was defined as appendicular lean soft tissue index by DXA. The EWGSOP1 and EWGSOP2 were applied and compared with McNemar tests and Cohen's kappa. All-cause mortality was analyzed with the Cox-proportional hazard model.Sarcopenia prevalence was 1.4-7.8% in 70-year-olds and 42-62% in 85years-old's, depending on diagnostic criteria. Overall, the prevalence of sarcopenia was 0.9-1.0 percentage points lower using the EWGSOP2 compared to EWGSOP1 when applying uniform T-score cut-offs (P<0.005). The prevalence was doubled (15.0 vs. 7.5%) using the -2.0 vs. -2.5T-scores with EWGSOP2 in the whole sample. The increase in prevalence when changing the cut-offs was 5.7% (P<0.001) in the 70-year-olds and 17.8% (P<0.001) in the 85-year-olds (EWGSP2). Sarcopenia with cut-offs at -2.5T-score was associated with increased mortality (hazard ratio 2.4-2.8, P<0.05) but not at T-score-2.0.The prevalence of sarcopenia was higher in 85-year-olds compared to 70-year-olds. Overall, the differences between the EWGSOP1 and EWGSOP2 classifications are small. Meaningful differences between EWGSOP1 and 2 in the 85-year-olds could not be ruled out. Prevalence was more dependent on cut-offs than on the operational definition.
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9.
  • Wetterberg, Hanna, et al. (författare)
  • Decreasing Incidence and Prevalence of Dementia Among Octogenarians: A Population-Based Study on 3 Cohorts Born 30 Years Apart
  • 2023
  • Ingår i: Journals of Gerontology Series a-Biological Sciences and Medical Sciences. - : Oxford University Press (OUP). - 1079-5006 .- 1758-535X. ; 78:6, s. 1069-1077
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Recent studies suggest a decline in the age-specific incidence and prevalence of dementia. However, results are mixed regarding trends among octogenarians. We investigated time trends in the prevalence and incidence of dementia in 3 population-based cohorts of 85-90-year olds. We also examined if there were different time trends for men and women. Methods We examined population-based birth cohorts within the Gothenburg H70 Birth Cohort Studies born 1901-02, 1923-24, and 1930, at ages 85 (N = 1481) and 88 (N = 840) years. The first 2 cohorts were also examined at age 90 (N = 450). The incidence was examined in 1 109 individuals free from dementia at baseline using information from the examination at age 88 or register data. All 3 cohorts were examined with identical methods. Results The prevalence of dementia decreased from 29.8% in 1986-87 to 21.5% in 2008-10 and 24.5% in 2015-16 among 85-year olds, and from 41.9% in 1989-90 to 28.0% in 2011-12 to 21.7% in 2018-19 among 88-year olds, and from 41.5% in 1991-92 to 37.2% in 2013-14 among 90-year olds. The decline was most accentuated among women. The incidence of dementia per 1 000 risk-years from ages 85 to 89 declined from 48.8 among those born 1901-02 to 37.9 in those born 1923-24 to 22.5 among those born 1930. Conclusions The prevalence and incidence of dementia decreased substantially over 3 decades among octogenarians. This might slow down the projected increase in cases of dementia expected by the increasing number of octogenarians during the following decades.
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10.
  • Wetterberg, Hanna, et al. (författare)
  • Dementia remains the major predictor of death among octogenarians. A study of two population cohorts of 85-year-olds examined 22 years apart
  • 2021
  • Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 36, s. 507-517
  • Tidskriftsartikel (refereegranskat)abstract
    • Dementia is the major predictor of death in old age. The aim of this paper was to determine whether 8-year mortality among 85-year olds with and without dementia, and if the contribution of dementia to mortality relative to other common diseases has changed. We used two population-based cohorts of 85-year-olds (N = 1065), born in 1901-02 and 1923-24, which were examined with identical methods in 1986-87 and 2008-2010 and followed for 8-year mortality according to data from the Swedish Tax Agency. Dementia was diagnosed according to DSM-III-R. Other diseases were diagnosed based on self-reports, close informant interviews, somatic examinations, and the Swedish National In-patient Register. Compared to cohort 1901-02, cohort 1923-24 had a lower 8-year mortality both among those with (HR 0.7; 95% CI 0.5-0.99) and without dementia (HR 0.7; 95% CI 0.5-0.9). Dementia was associated with increased mortality in both cohorts (cohort 1901-02, HR 2.6; 95% CI 2.0-3.2, cohort 1923-24, HR 2.8; 95% CI 2.3-3.5), and remained the major predictor of death, with a population attributable risk of 31.7% in 1986-87 and 27.7% in 2008-10. Dementia remained the most important predictor of death in both cohorts. The relative risk for mortality with dementia did not change between cohorts, despite a decreased mortality rate in the population.
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11.
  • Grönholdt Palm, Julia, et al. (författare)
  • Strategies to deal with information of different reliability exemplified by the use of QSARs to fill the algae data gaps in LCIAs of plastic additives
  • 2015
  • Ingår i: SETAC Europe 25th Annual Meeting.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Data gaps are problematic when screening fordangerous substances or in impact assessments where several chemicals are considered for evaluation. Lacking testing information can be replaced by non-testing information such as Quantitative Structure Activity Relationships (QSARs), but even though this latter information comes with lower reliability, this is seldom taken into account in theforthcoming assessments. The difficulty to meet standards for best information calls for strategies to handle data gaps which take varying reliability in information into account. Using safety factors when reliability is low can be problematic since this result in more conservative evaluations of substances for which information is of lowreliability and an unknown level of risk aversion in the assessment. An alternative is to reflect lower reliability using probability distributions representing the expected error in the information and propagate this uncertainty in the forthcoming assessments using Monte Carlo analysis.It is even possible to let the error to expect from QSARs depend to what extent a substance falls inside the models domain of applicability.QSARs cannot fill all gaps in data. Default values can be used instead of leaving substances out of assessments, but if so, these should reflect lowreliability as well. We demonstrate the practical implications of four strategies to handle varying reliability in information on algal toxicity in a Life Cycle Impact Assessment on 159 plastic additives of concernusing emissions from societal plastic materials in Sweden. A review concluded that a small amount of these substances had toxicity data for algae Pseudokirchneriella subcapitata. A QSAR was constructed which provided non-testing algal information of substances inside and on theborder of the models domain of applicability evaluated by PmodXPS.Substances with neither testing nor non-testing information were assigned default values. Screening based on characterization factors resulted in different rankings of substances when changing the level of cautiousness. The different strategies to handle varying reliability ininformation do more or less open up for quantifying uncertainty in Life Cycle Impact Assessments.
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12.
  • Harreither, E., et al. (författare)
  • Characterization of a novel cell penetrating peptide derived from human Oct4
  • 2014
  • Ingår i: Cell Regeneration. - : Springer Science and Business Media LLC. - 2045-9769. ; 3:2, s. 2-3:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Oct4 is a transcription factor that plays a major role for the preservation of the pluripotent state in embryonic stem cells as well as for efficient reprogramming of somatic cells to induced pluripotent stem cells (iPSC) or other progenitors. Protein-based reprogramming methods mainly rely on the addition of a fused cell penetrating peptide. This study describes that Oct4 inherently carries a protein transduction domain, which can translocate into human and mouse cells.A 16 amino acid peptide representing the third helix of the human Oct4 homeodomain, referred to as Oct4 protein transduction domain (Oct4-PTD), can internalize in mammalian cells upon conjugation to a fluorescence moiety thereby acting as a cell penetrating peptide (CPP). The cellular distribution of Oct4-PTD shows diffuse cytosolic and nuclear staining, whereas penetratin is strictly localized to a punctuate pattern in the cytoplasm. By using a Cre/loxP-based reporter system, we show that this peptide also drives translocation of a functionally active Oct4-PTD-Cre-fusion protein. We further provide evidence for translocation of full length Oct4 into human and mouse cell lines without the addition of any kind of cationic fusion tag. Finally, physico-chemical properties of the novel CPP are characterized, showing that in contrast to penetratin a helical structure of Oct4-PTD is only observed if the FITC label is present on the N-terminus of the peptide.Oct4 is a key transcription factor in stem cell research and cellular reprogramming. Since it has been shown that recombinant Oct4 fused to a cationic fusion tag can drive generation of iPSCs, our finding might contribute to further development of protein-based methods to generate iPSCs.Moreover, our data support the idea that transcription factors might be part of an alternative paracrine signalling pathway, where the proteins are transferred to neighbouring cells thereby actively changing the behaviour of the recipient cell.
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13.
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14.
  • Holmquist, Hanna, 1982, et al. (författare)
  • The potential to use QSAR to populate ecotoxicity characterisation factors for simplified LCIA and chemical prioritisation
  • 2018
  • Ingår i: International Journal of Life Cycle Assessment. - : Springer Science and Business Media LLC. - 1614-7502 .- 0948-3349. ; 23:11, s. 2208-2216
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Today’s chemical society use and emit an enormous number of different, potentially ecotoxic, chemicals to the environment. The vast majority of substances do not have characterisation factors describing their ecotoxicity potential. A first stage, high throughput, screening tool is needed for prioritisation of which substances need further measures. Methods: USEtox characterisation factors were calculated in this work based on data generated by quantitative structure-activity relationship (QSAR) models to expand substance coverage where characterisation factors were missing. Existing QSAR models for physico-chemical data and ecotoxicity were used, and to further fill data gaps, an algae QSAR model was developed. The existing USEtox characterisation factors were used as reference to evaluate the impact from the use of QSARs to generate input data to USEtox, with focus on ecotoxicity data. An inventory of chemicals that make up the Swedish societal stock of plastic additives, and their associated predicted emissions, was used as a case study to rank chemicals according to their ecotoxicity potential. Results and discussion: For the 210 chemicals in the inventory, only 41 had characterisation factors in the USEtox database. With the use of QSAR generated substance data, an additional 89 characterisation factors could be calculated, substantially improving substance coverage in the ranking. The choice of QSAR model was shown to be important for the reliability of the results, but also with the best correlated model results, the discrepancies between characterisation factors based on estimated data and experimental data were very large. Conclusions: The use of QSAR estimated data as basis for calculation of characterisation factors, and the further use of those factors for ranking based on ecotoxicity potential, was assessed as a feasible way to gather substance data for large datasets. However, further research and development of the guidance on how to make use of estimated data is needed to achieve improvement of the accuracy of the results.
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15.
  • Nordström, Moa, 1982, et al. (författare)
  • Pseudophakia and Lens Opacities in 70-Year-Olds in Gothenburg, Sweden; Gender Differences, Impact on Self-Reported Visual Function and Validation of Self-Reported Cataract and Pseudophakia
  • 2022
  • Ingår i: Clinical Ophthalmology. - 1177-5483. ; 16, s. 3269-3281
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: The study aimed at determining the prevalence and sex differences in cataract, pseudophakia, lens opacities and self -reported cataract in 70-year-old people in Gothenburg, Sweden. The purpose was also to identify correlations between lens opacities, visual acuity and subjective visual function, and to validate self-reported cataract and cataract surgery.Patients and Methods: Population-based cross-sectional study where participants (n=1182) answered questions about self-reported diagnosis of cataract and cataract surgery. A total of 1139 subjects completed the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25), 560 subjects underwent ophthalmic examination including visual acuity and lens photography. t-test, Pearson chi-square and Mann-Whitney U-test were used for obtaining p-values. ANOVA (analysis of variances, Kruskal- Wallis, one-way) was used to compare VFQ-25 between 3 groups; no cataract, cataract and pseudophakia. To clarify the differences between specific pairs of groups post-hoc test (Bonferroni) was used after ANOVA.Results: Self-reported cataract was more common in women than in men (27.2% vs 19.1%, p=0.001, chi-square). Cataract surgery was reported by 16.3% of women and 12.6% of men (p=0.072). Upon eye examination, the prevalence of pseudophakia was 16.9% in women compared to 10.2% in men (p=0.020). The prevalence of cataract, including pseudophakia, was 31.9% in women versus 23.8% in men (p=0.033). Significant correlations (Spearman's rho) were found between lens opacities and visual acuity. Self-reported cataract surgery showed a very high specificity and high sensitivity. The composite score from NEI VFQ-25 was lower in people with pseudophakia than in people with/without cataract (p=0.012, Kruskal-Wallis).Conclusion: The prevalence of cataract including pseudophakia in 70-year-olds in Gothenburg is higher compared to previous studies in similar geographical areas. Also, it is more common in women than in men. The lack of significant sex differences in lens opacities may be due to cataract surgery at an earlier stage. Validation showed very good agreement between pseudophakia and self-reported cataract surgery.
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16.
  • Novak, Masuma, 1969, et al. (författare)
  • Six-year mortality associated with living alone and loneliness in Swedish men and women born in 1930
  • 2023
  • Ingår i: BMC Geriatrics. - 1471-2318. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: This study examined how living alone and loneliness associate with all-cause mortality in older men and women. Methods: Baseline data from the Gothenburg H70 Birth Cohort Studies, including 70-year-olds interviewed in 2000 and 75-year-olds (new recruits) interviewed in 2005were used for analyses (N = 778, 353 men, 425 women). Six-year mortality was based on national register data. Results: At baseline, 36.6% lived alone and 31.9% reported feelings of loneliness. A total of 72 (9.3%) participants died during the 6-year follow-up period. Cumulative mortality rates per 1000 person-years were 23.9 for men and 9.6 for women. Mortality was increased more than twofold among men who lived alone compared to men living with someone (HR 2.40, 95% CI 1.34–4.30). Elevated risk remained after multivariable adjustment including loneliness and depression (HR 2.56, 95% CI 1.27–5.16). Stratification revealed that mortality risk in the group of men who lived alone and felt lonely was twice that of their peers who lived with someone and did not experience loneliness (HR 2.52, 95% CI 1.26–5.05). In women, a more than fourfold increased risk of mortality was observed in those who experienced loneliness despite living with others (HR 4.52, 95% CI 1.43–14.23). Conclusions: Living alone was an independent risk factor for death in men but not in women. Mortality was doubled in men who lived alone and felt lonely. In contrast, mortality was particularly elevated in women who felt lonely despite living with others. In the multivariable adjusted models these associations were attenuated and were no longer significant after adjusting for mainly depression in men and physical inactivity in women. Gender needs to be taken into account when considering the health consequences of living situation and loneliness.
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17.
  • Rydberg, Hanna, 1982, et al. (författare)
  • Effects of Tryptophan Content and Backbone Spacing on the Uptake Efficiency of Cell-Penetrating Peptides
  • 2012
  • Ingår i: Biochemistry. - : American Chemical Society (ACS). - 1520-4995 .- 0006-2960. ; 51:27, s. 5531-5539
  • Tidskriftsartikel (refereegranskat)abstract
    • Cell-penetrating peptides (CPPs) are able to traverse cellular membranes and deliver macromolecular cargo. Uptake occurs through both endocytotic and nonendocytotic pathways, but the molecular requirements for efficient internalization are not fully understood. Here we investigate how the presence of tryptophans and their position within an oligoarginine influence uptake mechanism and efficiency. Flow cytometry and confocal fluorescence imaging are used to estimate uptake efficiency, intracellular distribution and toxicity in Chinese hamster ovarian cells. Further, membrane leakage and lipid membrane affinity are investigated. The peptides contain eight arginine residues and one to four tryptophans, the tryptophans positioned either at the N-terminus, in the middle, or evenly distributed along the amino acid sequence. Our data show that the intracellular distribution varies among peptides with different tryptophan content and backbone spacing. Uptake efficiency is higher for the peptides with four tryptophans in the middle, or evenly distributed along the peptide sequence, than for the peptide with four tryptophans at the N-terminus. All peptides display low cytotoxicity except for the one with four tryptophans at the N-terminus, which was moderately toxic. This finding is consistent with their inability to induce efficient leakage of dye from lipid vesicles. All peptides have comparable affinities for lipid vesicles, showing that lipid binding is not a decisive parameter for uptake. Our results indicate that tryptophan content and backbone spacing can affect both the CPP uptake efficiency and the CPP uptake mechanism. The low cytotoxicity of these peptides and the possibilities of tuning their uptake mechanism are interesting from a therapeutic point of view.
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18.
  • Rydberg, Hanna, 1982 (författare)
  • Intracellular Uptake and Membrane Binding of Cell-penetrating Peptides: The Influence of Arginines, Tryptophans and Proteoglycans
  • 2011
  • Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • One of the major limitations in the realization of functional gene therapy is efficient intracellular transport of the therapeutic macromolecules. Amongst several different techniques, cell-penetrating peptides (CPPs) have emerged as promising candidates for this purpose. CPPs may cross cellular membranes by both endocytotic and non-endocytotic pathways, but the mechanisms by which uptake is mediated are not yet fully understood. It has been suggested that a major determinant in this issue is the interaction between the CPPs and the cell membrane, which is dependent on both the peptide sequence and membrane constituents. The focus of the work presented in this thesis is CPP-membrane interactions, and how they are influenced by the amino acids arginine and tryptophan, as well as by membrane proteoglycans. For this purpose cellular uptake and membrane affinity of penetratin and two homologues enriched in or lacking arginines were investigated in both wild type cells and cells lacking proteoglycans. Furthermore, uptake in live cells as well as induced liposome leakage and binding affinity to liposomes, of six newly designed peptides containing arginine and tryptophan in different combinations, were investigated. This was followed by investigating the orientation of the tryptophans and the secondary structure of these peptides when interacting with liposomes. We show that, with higher number of arginines both intracellular uptake and membrane affinity increase while the dependence of proteoglycans for uptake decreases. Moreover, we find that the spacing of tryptophans in the peptide sequence seems to influence intracellular uptake and that the variations in peptide secondary structure, as reflected by the angles of the transition moments of the tryptophans, also suggest variations in membrane interactions.
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19.
  • Rydberg, Hanna, 1982 (författare)
  • Membrane Active Arginine and Tryptophan Rich Peptides
  • 2013
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Genetic diseases, cancer and antibiotic resistant bacterial infections are causing many people a great deal of suffering every year. Treatment and cure of these medical conditions are desirable, but also challenging for the medical industry. Membrane-active peptides (MAPs) are a group of peptides that are very promising for all these medical applications. These peptides include the cell-penetrating peptides (CPPs) which have the ability to efficiently transport DNA, proteins and other macromolecules into cells, and the antimicrobial peptides (AMPs) that can kill or inhibit the growth of bacteria, fungi and parasites. The properties of these peptides are overlapping, and have been suggested to depend on both the peptide sequence and membrane constituents. The mechanisms of action of these peptides are, however, not yet fully understood. The goal with the work presented in this thesis, therefore is to better understand the mechanistic details of how membrane-active peptides bind to and interact with cellular membranes. The work focuses on the influence of the amino acids arginine and tryptophan on peptide function and membrane interaction, which has been investigated using cellular and physicochemical studies. The results from the work in this thesis indicate that the number and position of the amino acid tryptophan in the peptide sequence affect both cellular uptake and antibacterial properties. The biological effect seems partly related to the secondary structure of the peptides and the composition of the lipid membrane. The results also show that cellular uptake gains from increasing arginine content, and that proteoglycans at the cell surface specifically affect the cellular uptake of arginine-rich peptides. In addition, it is shown that the properties of the peptides may be affected by fluorescent labeling, and that this effect depends on the peptide amino acid sequence. In summary, these results give further information about how specific amino acids may affect the properties of the peptide, and how this regulates both membrane function and membrane specificity of membrane-active peptides.
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20.
  • Rydberg, Hanna, 1982, et al. (författare)
  • Membrane interaction and secondary structure of de novo designed arginine-and tryptophan peptides with dual function
  • 2012
  • Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 427:2, s. 261-265
  • Tidskriftsartikel (refereegranskat)abstract
    • Cell-penetrating peptides and antimicrobial peptides are two classes of positively charged membrane active peptides with several properties in common. The challenge is to combine knowledge about the membrane interaction mechanisms and structural properties of the two classes to design peptides with membrane-specific actions, useful either as transporters of cargo or as antibacterial substances. Membrane active peptides are commonly rich in arginine and tryptophan. We have previously designed a series of arg/trp peptides and investigated how the position and number of tryptophans affect cellular uptake. Here we explore the antimicrobial properties and the interaction with lipid model membranes of these peptides, using minimal inhibitory concentrations assay (MIC), circular dichroism (CD) and linear dichroism (LD). The results show that the arg/trp peptides inhibit the growth of the two gram positive strains Staphylococcus aureus and Staphylococcus pyogenes, with some individual variations depending on the position of the tryptophans. No inhibition of the gram negative strains Proteus mirabilis or Pseudomonas aeruginosa was noticed. CD indicated that when bound to lipid vesicles one of the peptides forms an a-helical like structure, whereas the other five exhibited rather random coiled structures. LD indicated that all six peptides were somehow aligned parallel with the membrane surface. Our results do not reveal any obvious connection between membrane interaction and antimicrobial effect for the studied peptides. By contrast cell-penetrating properties can be coupled to both the secondary structure and the degree of order of the peptides.
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21.
  •  
22.
  • Rydberg, Hanna, 1982, et al. (författare)
  • Peptide-membrane interactions of arginine-tryptophan peptides probed using quartz crystal microbalance with dissipation monitoring
  • 2014
  • Ingår i: European Biophysics Journal. - : Springer Science and Business Media LLC. - 1432-1017 .- 0175-7571. ; 43:6-7, s. 241-253
  • Tidskriftsartikel (refereegranskat)abstract
    • Membrane-active peptides include peptides that can cross cellular membranes and deliver macromolecular cargo as well as peptides that inhibit bacterial growth. Some of these peptides can act as both transporters and antibacterial agents. It is desirable to combine the knowledge from these two different fields of membrane-active peptides into design of new peptides with tailored actions, as transporters of cargo or as antibacterial substances, targeting specific membranes. We have previously shown that the position of the amino acid tryptophan in the peptide sequence of three arginine-tryptophan peptides affects their uptake and intracellular localization in live mammalian cells, as well as their ability to inhibit bacterial growth. Here, we use quartz crystal microbalance with dissipation monitoring to assess the induced changes caused by binding of the three peptides to supported model membranes composed of POPC, POPC/POPG, POPC/POPG/cholesterol or POPC/lactosyl PE. Our results indicate that the tryptophan position in the peptide sequence affects the way these peptides interact with the different model membranes and that the presence of cholesterol in particular seems to affect the membrane interaction of the peptide with an even distribution of tryptophans in the peptide sequence. These results give mechanistic insight into the function of these peptides and may aid in the design of membrane-active peptides with specified cellular targets and actions.
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23.
  • Rydberg, Tomas, 1962, et al. (författare)
  • Estimating the environmental risk of the societal stock of additives in plastics by a chemical footprint approach
  • 2015
  • Ingår i: SETAC Europe 25th Annual Meeting.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Environmental risk posed by additives in products in the technosphere in general and in consumer products in particular, is an important issue that has been, so far, investigated to a relatively limited extent. Previous estimates of the national stock and emissions are available on national scale [1,2,3] but the challenge has remained to understand how important or significant these stocks and emissions are from a risk perspective. The research presented here approaches the challenge by assigning risk characterisation scores to the additives and comparing the outcome with corresponding risk characterisation for biocides. We used the previous estimates om stock and emissions of plastic additives. Data for use of biocides were extracted from the Swedish Chemicals Agency The risk characterisation was carried out by applying USETox characterisation factors (CF), The amount of each substance, has been multiplied with its corresponding CF from USETox. These substance specific risk scores were then added to the overall risk score. It is clear that there are many uncertainties in the calculations. For example the emission calculations in the overall society example seem unreasonably high, in the order of 2 % annually of the total stock. In other work applying an advanced emission model to a limited sample of products, the emission rate is in the order of 0.02 % annually. This indicates that the overall society-wide emissions could be in the order of 500 tons rather than 47000 tons. For the risk scores, the uncertainty is even bigger, as the uncertainty of the CFs themselves come into play, as well as the incomplete availability of CFs. The total risk score for the National total use of biocides is 9.3E+09 CTU. This is to be compared with the risk scores as calculated for the additives, which is 1.3E+12 CTU for the total stock of additives and 3E+10 CTU for the emissions, or possible a factor 100 lower if assuming a similar overestimation as for emissions. The results are very sensitive to the identified uncertainties, and also to lack of CFs for possibly important substances, both among the additives and the biocides.
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24.
  • Åmand, Helene, 1983, et al. (författare)
  • Cell surface binding and uptake of arginine- and lysine-rich penetratin peptides in absence and presence of proteoglycans
  • 2012
  • Ingår i: Biochimica et Biophysica Acta - Biomembranes. - : Elsevier BV. - 1879-2642 .- 0005-2736. ; 1818:11, s. 2669-2678
  • Tidskriftsartikel (refereegranskat)abstract
    • Cell surface proteoglycans (PGs) appear to promote uptake of arginine-rich cell-penetrating peptides (CPPs), but their exact functions are unclear. To address if there is specificity in the interactions of arginines and PGs leading to improved internalization, we used flow cytometry to examine uptake in relation to cell surface binding for penetratin and two arginine/lysine substituted variants (PenArg and PenLys) in wildtype CHO-K1 and PG-deficient A745 cells. All peptides were more efficiently internalized into CHO-K1 than into A745. but their cell surface binding was independent of cell type. Thus, PGs promote internalization of cationic peptides, irrespective of the chemical nature of their positive charges. Uptake of each peptide was linearly dependent on its cell surface binding, and affinity is thus important for efficiency. However, the gradients of these linear dependencies varied significantly. Thus each peptide's ability to stimulate uptake once bound to the cell surface is reliant on formation of specific uptake-promoting interactions. Heparin affinity chromatography and clustering experiments showed that penetratin and PenArg binding to sulfated sugars is stabilized by hydrophobic interactions and result in clustering, whereas PenLys only interacts through electrostatic attraction. This may have implications for the molecular mechanisms behind arginine-specific uptake stimulation as penetratin and PenArg are more efficiently internalized than PenLys upon interaction with PGs. However, PenArg is also least affected by removal of PGs. This indicates that an increased arginine content not only improve PG-dependent uptake but also that PenArg is more adaptable as it can use several portals of entry into the cell.
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