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1.
  • Jiang, Zheshun, et al. (author)
  • Hexavalent chromium still a concern in Sweden : Evidence from a cross-sectional study within the SafeChrom project
  • 2024
  • In: International journal of hygiene and environmental health. - : Elsevier. - 1438-4639 .- 1618-131X. ; 256
  • Journal article (peer-reviewed)abstract
    • ObjectivesHexavalent chromium (Cr(VI)) is classified as a human carcinogen. Occupational Cr(VI) exposure can occur during different work processes, but the current exposure to Cr(VI) at Swedish workplaces is unknown.MethodsThis cross-sectional study (SafeChrom) recruited non-smoking men and women from 14 companies with potential Cr(VI) exposure (n = 113) and controls from 6 companies without Cr(VI) exposure (n = 72). Inhalable Cr(VI) was measured by personal air sampling (outside of respiratory protection) in exposed workers. Total Cr was measured in urine (pre- and post-shift, density-adjusted) and red blood cells (RBC) (reflecting Cr(VI)) in exposed workers and controls. The Bayesian tool Expostats was used to assess risk and evaluate occupational exposure limit (OEL) compliance.ResultsThe exposed workers performed processing of metal products, steel production, welding, plating, and various chemical processes. The geometric mean concentration of inhalable Cr(VI) in exposed workers was 0.15 μg/m3 (95% confidence interval: 0.11–0.21). Eight of the 113 exposed workers (7%) exceeded the Swedish OEL of 5 μg/m3, and the Bayesian analysis estimated the share of OEL exceedances up to 19.6% for stainless steel welders. Median post-shift urinary (0.60 μg/L, 5th-95th percentile 0.10–3.20) and RBC concentrations (0.73 μg/L, 0.51–2.33) of Cr were significantly higher in the exposed group compared with the controls (urinary 0.10 μg/L, 0.06–0.56 and RBC 0.53 μg/L, 0.42–0.72). Inhalable Cr(VI) correlated with urinary Cr (rS = 0.64) and RBC-Cr (rS = 0.53). Workers within steel production showed the highest concentrations of inhalable, urinary and RBC Cr. Workers with inferred non-acceptable local exhaustion ventilation showed significantly higher inhalable Cr(VI), urinary and RBC Cr concentrations compared with those with inferred acceptable ventilation. Furthermore, workers with inferred correct use of respiratory protection were exposed to significantly higher concentrations of Cr(VI) in air and had higher levels of Cr in urine and RBC than those assessed with incorrect or no use. Based on the Swedish job-exposure-matrix, approximately 17 900 workers were estimated to be occupationally exposed to Cr(VI) today.ConclusionsOur study demonstrates that some workers in Sweden are exposed to high levels of the non-threshold carcinogen Cr(VI). Employers and workers seem aware of Cr(VI) exposure, but more efficient exposure control strategies are required. National strategies aligned with the European strategies are needed in order to eliminate this cause of occupational cancer.
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  • Jiang, Zheshun, et al. (author)
  • P-205 THE SAFECHROM PROJECT - EVIDENCE FROM A CROSS-SECTIONAL STUDY SHOWS THAT HEXAVALENT CHROMIUM IS STILL A CONCERN IN SWEDEN
  • 2024
  • In: Occupational Medicine. - 0962-7480. ; 74:Suppl 1, s. 291-292
  • Conference paper (other academic/artistic)abstract
    • Hexavalent chromium Cr(VI) is a human carcinogen, but the current exposure to Cr(VI) at Swedish workplaces is unknown.Recruitment of 113 workers with potential Cr(VI) exposure and 72 controls was combined with measurements of inhalable Cr(VI) (only exposed workers) and total Cr in urine and red blood cells (RBC), Bayesian analysis of occupational exposure limit (OEL) compliance was used, as well as the Swedish job-exposure-matrix.Exposed workers performed processing of metal products, steel production, welding, and plating. The geometric mean concentration of inhalable Cr(VI) in exposed workers was 0.15 μg/m3. Eight workers (7\ exceeded the Swedish OEL (5 μg/m3), and the share of OEL exceedances was estimated to be up to 19.6\ and RBC-Cr were significantly higher in exposed workers compared with controls. Workers with inferred non-acceptable local exhaustion ventilation showed significantly higher inhalable Cr(VI), urine- and RBC-Cr than those with acceptable ventilation. Workers with inferred correct use of respiratory protection had higher inhalable Cr(VI), and, paradoxically, higher urine- and RBC-Cr concentrations than workers with incorrect use. We estimate that ~17 900 Swedish workers are occupationally exposed to Cr(VI) today.Our study showed that although most air measurements were relatively low, 7\ and particularly stainless steel workers are at risk for exceeding the OEL. The existing protective measures implemented at workplaces are still inadequate and insufficient.Some workers in Sweden are exposed to high levels of the non-threshold carcinogen Cr(VI). National strategies aligned with European strategies are needed to eliminate occupational cancer.
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3.
  • Ljunggren, Mirjam, et al. (author)
  • Association between proteomics and obstructive sleep apnea phenotypes in a community-based cohort of women
  • 2020
  • In: Journal of Sleep Research. - : John Wiley & Sons. - 0962-1105 .- 1365-2869. ; 29:4
  • Journal article (peer-reviewed)abstract
    • Proteomic‐based technologies offer new opportunities to identify proteins that might reflect the cardiometabolic stress caused by different aspects of sleep‐disordered breathing. We aimed to investigate whether severe obstructive sleep apnea and severe obstructive sleep apnea during rapid eye movement sleep are associated with changed levels of inflammatory and cardiac disease‐related proteins in a population‐based cohort of women. In the community‐based “Sleep and Health in Women” (SHE) cohort study, 400 women underwent polysomnography, anthropometric measurements and blood sampling. Two proteomic assays (Olink Proseek® Inflammation panel and Olink Proseek® Cardiovascular II panel), each measuring 92 proteins, were analysed in a subsample of 253 women. p‐Values were adjusted for multiple testing, with false discovery rate set at 10%. In unadjusted models, 57 proteins were associated with apnea−hypopnea index, 56 proteins with oxygen desaturation index and 64 proteins with rapid eye movement−apnea−hypopnea index. After adjustment for age, body mass index and plate, there were no significant associations between apnea−hypopnea index or oxygen desaturation index and any of the proteins. Severe obstructive sleep apnea during rapid eye movement sleep (rapid eye movement−apnea−hypopnea index ≥ 30) was associated with decreased levels of two anti‐inflammatory proteins; Sirt2 (q‐value .016) and LAP‐TGF‐β1 (q‐value .016). There was also a negative association between rapid eye movement−apnea−hypopnea index of ≥ 30 and Axin1 (q‐value .095), a protein thought to facilitate TGF‐β‐signalling. We conclude that severe obstructive sleep apnea during rapid eye movement sleep is associated with low levels of Sirt2, LAP‐TGF‐β1 and Axin1, anti‐inflammatory proteins involved in metabolic regulation and in the atherosclerotic process. For obstructive sleep apnea based on a whole night, the associations with cardiac and inflammatory proteins are weaker, and explained to a large extent by age and body mass index.
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  • Ljunggren, Mirjam (author)
  • Sleep-disordered breathing in women : Associations with cardiovascular disease and the significance of sleep apnea during REM sleep
  • 2019
  • Doctoral thesis (other academic/artistic)abstract
    • Background: Sleep-disordered breathing (SDB) is associated with an increased risk of cardiovascular disease, but it is unclear which elements of SDB that are most harmful to the cardiovascular system and whether the associations observed in men also apply to women.Aim: To investigate associations between different aspects of SDB and cardiovascular disease in womenMethods and results: All four papers were based on participants in “Sleep and Health in Women” (SHE), a population-based cohort study of women.Paper I is a cross-sectional study of 349 women with polysomnographic assessments of obstructive sleep apnea (OSA) and measurements of plasma BNP, clinically used as a marker of heart failure, in the morning. There was a dose-response relationship between the severity of OSA and levels of BNP.In Paper II, with a study population of 5,990 women, questionnaire data on symptoms of obstructive sleep apnea were combined with register data from the Swedish National Patient Register regarding a diagnosis of heart failure (mean follow-up 11.4 years). Women with the combination of snoring and daytime sleepiness had a two-fold increase in the risk of incident heart failure after adjustment for confounding.Paper III was based on 201 women without known cardiovascular disease, with a polysomnography at baseline, assessing OSA during REM sleep, and a carotid artery ultrasound with measurements of intima thickness at follow-up. Severe OSA during REM sleep was associated with a thicker carotid intima.Paper IV comprised 253 women with polysomnographic data on severe OSA and severe OSA during REM sleep, as well as proteomic analyses of cardiac and inflammatory proteins. After adjustment for confounding and multiple testing, severe OSA during REM sleep was associated with decreased levels of Sirt2, LAP-TGF-β1 and Axin1, while there were no significant associations for OSA based on a whole night and protein levels.Conclusions: Women with symptoms of OSA run an increased risk of developing heart failure and OSA is associated with increased levels of BNP. Severe OSA during REM sleep is associated with an early sign of atherosclerosis and reduced levels of proteins with anti-inflammatory effects linked to atherosclerosis and metabolic regulation.
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6.
  • Abelev, Betty, et al. (author)
  • Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
  • 2013
  • In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
  • Journal article (peer-reviewed)abstract
    • Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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7.
  • Amid Hägg, Shadi, 1982- (author)
  • Sleep disturbances : Consequences and comorbidities
  • 2021
  • Doctoral thesis (other academic/artistic)abstract
    • Background: Sleep disorders are common in the general population, with insomnia and sleep-related breathing disorders being the most common disorders. Since sleep has many important functions, such as a role in consolidation of memories and learning, energy conservation, cardiovascular and immune system regulation, it is not surprising that the disruption of normal sleep may lead to negative health effects and various comorbidities.  Aim: The overall aim of this thesis was to investigate the impact of disturbed sleep on various consequences and comorbidities. Methods and results: Papers I and II were based on the Sleep and Health in Women (SHE), a population-based prospective study of women, where a questionnaire was sent to women in 2000 and 2010. In paper I, the study cohort comprised 4,320 women <67 years of age who answered both questionnaires and had worked during the follow-up period. In women, having a long history of insomnia symptoms was associated with an increased risk of self-reported occupational accidents.In paper II, the 4,882 participants who answered the questions regarding nocturnal gastroesophageal reflux and snoring in both questionnaires were included in the study cohort. Women with nocturnal gastroesophageal reflux and snoring were at an increased risk of developing daytime sleepiness and to involuntarily fall asleep during the day. Paper III was based on the RHINE-cohort with participants from seven Northern European centers. The study cohort in paper III comprised the 2,568 smokers in the baseline study that also reported being smokers or former smokers in the follow-up study. It was found that having insomnia symptoms or excessive daytime sleepiness decreases the chance of long-term smoking cessation, and that smoking increases the risk of incident difficulties inducing sleep. Paper IV was the population-based, cross-sectional GA2LEN-survey which was conducted in four major Swedish cities. Paper IV included the 25,901 participants who answered questions regarding both snoring and insomnia symptoms. The combination of snoring and insomnia symptoms was associated with an increased risk of hypertension, asthma, chronic obstructive pulmonary disease, and daytime sleepiness. Conclusions: Disturbed sleep, due to varying causes, influences the risk of occupational accidents, on the chance of successful smoking cessation, on the risk of daytime sleepiness, hypertension, and obstructive lung disease. In clinical consultation, it is important to always inquire about disturbed sleep as it can have an impact on many aspects of health.  
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  • Amid Hägg, Shadi, et al. (author)
  • Smokers with insomnia symptoms are less likely to stop smoking
  • 2020
  • In: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 170
  • Journal article (peer-reviewed)abstract
    • Objectives: Smoking is associated with sleep disturbances. The aim of this study was to analyze whether sleep disturbances are predictors of smoking cessation and whether continued smoking is associated with the development of sleep disturbances. Methods: A questionnaire was sent to randomly selected men and women in Northern Europe in 1999-2001 (RHINE II) and was followed up by a questionnaire in 2010-2012 (RHINE III). The study population consisted of 2568 participants who were smokers at baseline and provided data on smoking at follow-up. Insomnia symptoms were defined as having difficulty initiating and/or maintaining sleep and/or early morning awakening >= 3 nights/week. Multiple logistic regression analyses were performed to calculate odds ratios (OR). Results: Subjects with difficulty initiating sleep (adjusted odds ratio; 95% confidence interval: 0.6; 0.4-0.8), difficulty maintaining sleep (0.7; 0.5-0.9), early morning awakening (0.6; 0.4-0.8), any insomnia symptom (0.6; 0.5-0.8) or excessive daytime sleepiness (0.7; 0.5-0.8) were less likely to achieve long-term smoking cessation after adjustment for age, BMI, pack-years, hypertension, diabetes, chronic bronchitis, rhinitis, asthma, gender and BMI difference. There was no significant association between snoring and smoking cessation. In subjects without sleep disturbance at baseline, continued smoking increased the risk of developing difficulty initiating sleep during the follow-up period compared with those that had quit smoking (adj. OR 1.7, 95% CI 1.2-2.3). Conclusions: Insomnia symptoms and excessive daytime sleepiness negatively predict smoking cessation. Smoking is a risk factor for the development of difficulty initiating sleep. Treatment for sleep disturbances should be included in smoking-cessation programs.
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  • Amid Hägg, Shadi, et al. (author)
  • The negative health effects of having a combination of snoring and insomnia
  • 2022
  • In: JOURNAL OF CLINICAL SLEEP MEDICINE. - : American Academy of Sleep Medicine (AASM). - 1550-9389 .- 1550-9397. ; 18:4, s. 973-981
  • Journal article (peer-reviewed)abstract
    • Study Objectives: Insomnia and snoring are common sleep disorders. The aim was to investigate the association of having a combination of insomnia symptoms and snoring with comorbidity and daytime sleepiness. Methods: The study population comprised 25,901 participants (16-75 years, 54.4% women) from 4 Swedish cities, who answered a postal questionnaire that contained questions on snoring, insomnia symptoms (difficulties initiating and/or maintaining sleep and/or early morning awakening), smoking, educational level, and respiratory and nonrespiratory disorders. Results: Snoring was reported by 4,221 (16.2%), while 9,872 (38.1%) reported 1 insomnia symptom. A total of 2,150 (8.3%) participants reported both insomnia symptoms and snoring. The association with hypertension (adjusted odds ratio [OR], 1.4; 95% confidence interval [Cl], 1.2-1.6), chronic obstructive pulmonary disease (adjusted OR, 1.8; 95% CI, 1.3-2.4), asthma (adjusted OR, 1.9; 95% CI, 1.6-2.3), daytime sleepiness (adjusted OR, 7.9; 95% CI, 7.1-8.8), and the use of hypnotics (adjusted OR, 7.5; 95% CI, 6.1-9.1) was highest for the group with both insomnia symptoms and snoring. Conclusions: Participants with both snoring and insomnia run an increased risk of hypertension, chronic obstructive pulmonary disease, asthma, daytime sleepiness, and use of hypnotics. It is important to consider snoring in patients seeking medical assistance for insomnia and, vice versa, in patients with snoring inquiring about insomnia.
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  • Benedict, Christian, Docent, 1976-, et al. (author)
  • Sex-specific association of the lunar cycle with sleep
  • 2022
  • In: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 804
  • Journal article (peer-reviewed)abstract
    • Using one-night sleep recordings from 852 subjects all living in Uppsala, Sweden, the present study represents one of the largest polysomnography investigations into the association of the 29.53-day long lunar cycle with sleep among men and women and across a wide age range (22–81 years). Following the day after the new moon until the day of the full moon (also named the waxing period), the moon's illumination increases, and the timing of the meridian of the moon is gradually shifted from noontime toward midnight. In contrast, from the day after the full moon until the day of the new moon (also named the waning period), the moon's illumination decreases, and the timing of the meridian of the moon is gradually shifted from early night hours toward noontime. Thus, we focused on the contrast between the waxing and waning periods. Sleep duration was shorter on nights during the waxing period as compared to waning period (P < 0.001). In addition, a significant interaction effect of participants' sex with the lunar period on sleep was noted (P < 0.05). Men, but not women, exhibited lower sleep efficiency (P < 0.001 and P = 0.748, respectively) and were longer awake after sleep onset (P = 0.010 and P = 0.890, respectively) on nights during the waxing period. All associations were robust to adjustment for confounders (including regular sleep disturbances). Our findings suggest that the effects of the lunar cycle on human sleep are more pronounced among men. Based on the cross-sectional design of the study, no firm conclusions can be drawn on the causality of the relations.
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  • Beziat, Vivien, et al. (author)
  • NK cell responses to cytomegalovirus infection lead to stable imprints in the human KIR repertoire and involve activating KIRs
  • 2013
  • In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 121:14, s. 2678-2688
  • Journal article (peer-reviewed)abstract
    • Human natural killer (NK) cells are functionally regulated by killer cell immunoglobulin-like receptors (KIRs) and their interactions with HLA class I molecules. As KIR expression in a given NK cell is genetically hard-wired, we hypothesized that KIR repertoire perturbations reflect expansions of unique NK-cell subsets and may be used to trace adaptation of the NK-cell compartment to virus infections. By determining the human KIR-ome at a single-cell level in more than 200 donors, we were able to analyze the magnitude of NK cell adaptation to virus infections in healthy individuals. Strikingly, infection with human cytomegalovirus (CMV), but not with other common herpesviruses, induced expansion and differentiation of KIR-expressing NK cells, visible as stable imprints in the repertoire. Education by inhibitory KIRs promoted the clonal-like expansion of NK cells, causing a bias for self-specific inhibitory KIRs. Furthermore, our data revealed a unique contribution of activating KIRs (KIR2DS4, KIR2DS2, or KIR3DS1), in addition to NKG2C, in the expansion of human NK cells. These results provide new insight into the diversity of KIR repertoire and its adaptation to virus infection, suggesting a role for both activating and inhibitory KIRs in immunity to CMV infection.
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  • Björk, Anne, et al. (author)
  • Variations in the vitamin D receptor gene are not associated with measures of muscle strength, physical performance, or falls in elderly men : Data from MrOS Sweden
  • 2019
  • In: Journal of Steroid Biochemistry and Molecular Biology. - : Elsevier BV. - 0960-0760 .- 1879-1220. ; 187, s. 160-165
  • Journal article (peer-reviewed)abstract
    • The vitamin D receptor (VDR) has been proposed as a candidate gene for several musculoskeletal phenotypes. However, previous results on the associations between genetic variants of the VDR with muscle strength and falls have been contradictory. The MrOS Sweden survey, a prospective population-based cohort study of 3014 elderly men (mean age 75 years, range 69-81) offered the opportunity to further investigate these associations. At baseline, data were collected on muscle strength and also the prevalence of falls during the previous 12 months. Genetic association analysis was performed for 7 Single Nucleotide Polymorphisms (SNPs), covering the genetic region surrounding the VDR gene in 2924 men with available samples of DNA. Genetic variations in the VDR were not associated with five different measurements of muscle strength or physical performance (hand grip strength right and left, 6 m walking test (easy and narrow) and timed-stands test). However, one of the 7 SNPs of the gene for the VDR receptor, rs7136534, was associated with prevalence of falls (33.6% of the AA, 14.6% of the AG and 16.5% of the GG allele). In conclusion, VDR genetic variants are not related to muscle strength or physical performance in elderly Swedish men. The role of the rs7136534 SNP for the occurrence of falls is not clear.
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  • Bornefalk, Eva, et al. (author)
  • Age-dependent effect of oral glucocorticoids on markers of bone resorption in patients with acute asthma
  • 1998
  • In: Calcified Tissue International. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 63:1, s. 9-13
  • Journal article (peer-reviewed)abstract
    • It is generally accepted that bone formation is depressed during corticosteroid treatment, but the effects of glucocorticoids on bone resorption are less well characterized. We have investigated the effects of short-term treatment with high-dose oral glucocorticoids on biochemical markers of bone turnover in 20 consecutive patients with asthma who sought help for acute respiratory obstruction in our emergency department. Serum concentrations of the carboxy-terminal cross-linked telopeptide of type 1 collagen (1CTP), reflecting bone resorption, and the carboxy-terminal propeptide of type 1 procollagen (P1CP), reflecting bone formation, were measured by radioimmunoassay. Changes of the circulating levels of the bone resorption marker 1CTP after treatment were age dependent with a significant negative correlation (r = -0.54, P = 0.01). The dependency on age remained when correcting, in a multiple linear regression analysis, for 1CTP levels at admission, weight, sex, and daily maintenance dose of inhaled glucocorticoids. Circulating levels of P1CP were suppressed in the whole group 1 week after initiation of glucocorticoid therapy, from 123.3 +/- 10.2 ng/ml at admission to 88.1 +/- 6.3 ng/ml after 1 week (P < 0.01). The changes in P1CP levels were not related to age. Our data indicate that bone formation is suppressed by glucocorticoids in all age groups, whereas the effect of glucocorticoids on markers of bone resorption is dependent on age.
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  • Clewemar, Pantelis, et al. (author)
  • Expanding the phenotypic spectrum of osteogenesis imperfecta type V including heterotopic ossification of muscle origins and attachments
  • 2019
  • In: Molecular Genetics & Genomic Medicine. - : Wiley. - 2324-9269. ; 7:7
  • Journal article (peer-reviewed)abstract
    • BackgroundOsteogenesis imperfecta (OI) is a clinical and genetic heterogeneous group of connective tissue disorders, characterized by bone fragility and a propensity to fracture.MethodsIn this report we describe the clinical phenotype of two patients, a 28‐year‐old woman and her mother (54 years old), both with a history of short stature and multiple fractures.ResultsExome sequencing revealed the recurring IFITM5:c.‐14 C>T variant causing OI type V. Both patients had several fractures during childhood. CT‐scan and scintigraphy showed ossification of the origin and attachment of muscles and hypertrophic callus formation.ConclusionOssification of the origin and attachment of muscles seems to be part of the phenotype in patients with OI type V.
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  • Danesh, Noushin, et al. (author)
  • Development of criteria for investigation of periapical tissue from root-filled teeth.
  • 2019
  • In: Acta Odontologica Scandinavica. - : Taylor & Francis. - 0001-6357 .- 1502-3850. ; 77:4, s. 269-274
  • Journal article (peer-reviewed)abstract
    • Objective: To develop and assess a set of criteria to grade inflammation including relative area of inflammation in periapical lesions in endodontically treated teeth. Material and methods: A set of criteria was developed, encompassing data on: Lymphocytes, denoting chronic inflammation, were graded 0 (occasional) to 4 (heavy/dense inflammation). Polymorphonuclear cells, denoting acute inflammation, were graded 0 (none) to 2 (many). The third parameter, area of inflammation, that is, the relative area of the specimen that was inflamed, was graded 0 (none) to 4 (76–100%). The criteria were tested on 199 consecutive biopsies from 180 patients (aged 31–75 years). Information about symptoms was retrieved from the referrals. Mann–Whitney’s U-test was used to calculate possible differences in average values for the histopathological variables in the two groups of patients: symptomatic or asymptomatic. Results: Using the criteria, varying grades of inflammation were seen in the biopsies. The majority showed few or no PMN cells. There was a correlation between symptoms and the extent of infiltration of lymphocytes and plasma cells (p = .001), PMN cells (p < .001) and the area of inflammation (p = .002): biopsies from the asymptomatic patients exhibited less pronounced and relatively smaller areas of inflammation. Conclusions: Using the criteria on a specific selection of root-filled teeth with persisting apical periodontitis, periapical inflammation was common, but varied in extent and severity. The inflammation was less pronounced and affected a relatively smaller area in asymptomatic teeth, although outliers in both directions were identified.
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  • Doverskog, Magnus, et al. (author)
  • Cell cycle progression in serum-free cultures of Sf9 insect cells : Modulation by conditioned medium factors and implications for proliferation and productivity
  • 2000
  • In: Biotechnology progress (Print). - : Wiley. - 8756-7938 .- 1520-6033. ; 16:5, s. 837-846
  • Journal article (peer-reviewed)abstract
    • Cell cycle progression was studied in serum-free batch cultures of Spodoptera frugiperda (Sf9) insect cells, and the implications for proliferation and productivity were investigated. Cell cycle dynamics in KBM10 serum-free medium was characterized by an accumulation of 50-70% of the cells in the G(2)/M phase of the cell cycle during the first 24 h after inoculation. Following the cell cycle arrest, the cell population was redistributed into G(1) and in particular into the S phase. Maximum rate of proliferation (mu(N,max)) was reached 24-48 h after the release from cell cycle arrest, coinciding with a minimum distribution of cells in the G(2)/M phase. The following declining mu(N) could be explained by a slow increase in the G(2)/M cell population. However, at approximately 100 h, an abrupt increase in the amount of G(2)/M cells occurred. This switch occurred at about the same time point and cell density, irrespective of medium composition and maximum cell density. An octaploid population evolved from G(2)/M arrested cells, showing the occurrence of endoreplication in this cell line. In addition, conditioned medium factor(s) were found to increase mu(N,max), decrease the time to reach mu(N,max), and decrease the synchronization of cells in G(2)/M during the lag and growth phase. A conditioned medium factor appears to be a small peptide. On basis of these results we suggest that the observed cell cycle dynamics is the result of autoregulatory events occurring at key points during the course of a culture, and that entry into mitosis is the target for regulation. Infecting the Sf9 cells with recombinant baculovirus resulted in a linear increase in volumetric productivity of beta-galactosidase up to 68-75 h of culture. Beyond this point almost no product was formed. Medium renewal at the time of infection could only partly restore the lost hypertrophy and product yield of cultures infected after the transition point. The critical time of infection correlated to the time when the mean;population cell volume had attained a minimum, and this occurred 24 h before the switch into the G(2)/M phase. We suggest that the cell density dependent decrease in productivity ultimately depends on the autoregulatory events leading to G(2)/M cell cycle arrest.
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  • Emilsson, Össur Ingi, et al. (author)
  • Association between lung function decline and obstructive sleep apnoea: the ALEC study
  • 2021
  • In: Sleep and Breathing. - : Springer Science and Business Media LLC. - 1520-9512 .- 1522-1709. ; 25, s. 587-596
  • Journal article (peer-reviewed)abstract
    • Purpose To study changes in lung function among individuals with a risk of obstructive sleep apnoea (OSA), and if asthma affected this relationship. Methods We used data from the European Community Respiratory Health Survey II and III, a multicentre general population study. Participants answered questionnaires and performed spirometry at baseline and 10-year follow-up (n= 4,329 attended both visits). Subjects with high risk for OSA were identified from the multivariable apnoea prediction (MAP) index, calculated from BMI, age, gender, and OSA symptoms at follow-up. Asthma was defined as having doctor's diagnosed asthma at follow-up. Primary outcomes were changes in forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) from baseline to follow-up. Results Among 5108 participants at follow-up, 991 (19%) had a high risk of OSA based on the MAP index. Participants with high OSA risk more often had wheeze, cough, chest tightness, and breathlessness at follow-up than those with low OSA risk. Lung function declined more rapidly in subjects with high OSA risk (low vs high OSA risk [mean +/- SD]: FEV1 = - 41.3 +/- 24.3 ml/year vs - 50.8 +/- 30.1 ml/year; FVC = - 30.5 +/- 31.2 ml/year vs - 45.2 +/- 36.3 ml/year). Lung function decline was primarily associated with higher BMI and OSA symptoms. OSA symptoms had a stronger association with lung function decline among asthmatics, compared to non-asthmatics. Conclusion In the general population, a high probability of obstructive sleep apnoea was related to faster lung function decline in the previous decade. This was driven by a higher BMI and more OSA symptoms among these subjects. The association between OSA symptoms and lung function decline was stronger among asthmatics.
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  • Emilsson, Össur Ingi, et al. (author)
  • Insufficient sleep and new onset of nocturnal gastroesophageal reflux among women : a longitudinal cohort study
  • 2022
  • In: Journal of Clinical Sleep Medicine (JCSM). - : American Academy of Sleep Medicine (AASM). - 1550-9389 .- 1550-9397. ; 18:7, s. 1731-1737
  • Journal article (peer-reviewed)abstract
    • Study Objectives: Whether short or insufficient sleep are risk factors for new-onset nocturnal gastroesophageal reflux (nGER). Methods: In this 10-year longitudinal study, adult general-population women in Uppsala, Sweden, answered questionnaires on sleep, nGER, and other conditions on 2 occasions. Participants at baseline totaled 6,790, while participants at follow-up totaled 4,925. "Short sleep" was defined as sleeping < 6 hours/night and "insufficient sleep" was defined as reporting an average actual sleep duration below 80% of the self-estimated need for sleep duration but without "short sleep." nGER was defined as reporting heartburn or acid reflux after going to bed sometimes, often, or very often. The confounding factors-age, body mass index, physical activity, caffeine intake, smoking habits, alcohol dependence, depression, anxiety, and snoring-were defined from the questionnaire. Results: At baseline, 839 participants reported short sleep and 1,079 participants were defined as having insufficient sleep. Both participants with insufficient sleep and short sleep had nGER more often than those with sufficient sleep (26% vs 17% vs 10%, respectively). At follow-up, a new onset of nGER was twice as common among those with insufficient or short sleep at baseline and follow-up, compared with those with sufficient sleep at baseline and follow-up, even after adjusting for confounding factors (odds ratio 2.0 [1.5-2.8], P <.001). Conclusions: Insufficient sleep and short sleep are associated with nGER. Persistent insufficient and/or short sleep independently increases the risk of developing nGER over a 10-year follow-up. Women seeking treatment for nGER should be questioned about their sleep habits to identify insufficient sleep as a possible causative factor.
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24.
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25.
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26.
  • Grundberg, Elin, et al. (author)
  • A TA-repeat polymorphism in the gene for the estrogen receptor alpha does not correlate with muscle strength or body composition in young adult Swedish women.
  • 2005
  • In: Maturitas. - 0378-5122. ; 50:3, s. 153-60
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: There are conflicting data in the literature whether estrogens affect muscle strength. Prospective studies with hormone replacement therapy have not been able to convincingly demonstrate a muscular effect and the putative role of estrogen in the development of lean body mass is not established. Both lean mass and fat mass are known to be under strong genetic control and therefore we have investigated the relation between a TA-repeat in the gene for the estrogen receptor alpha (ERalpha) and muscle strength and body composition. METHODS: 175 healthy Swedish women, aged 20-39 were randomly selected from the population registry and included in the study. Body mass measurements (lean mass, fat mass, body weight and BMI) and muscle strength (quadriceps, hamstring and grip strength) were evaluated. The TA-repeat in the ERalpha gene was amplified by polymerase chain reaction. RESULTS: Alleles with a TA-repeat length of 16 repeats or shorter were denoted short (e), and repeat length of 17 repeats or longer were denoted long (E). Women homozygous for the short and long genotype were denoted ee (31%) and EE (21%), respectively, while heterozygous individuals were denoted Ee (48%). The frequencies were in Hardy-Weinberg equilibrium. No associations were found between ERalpha genotypes and muscle strength or body composition. CONCLUSION: The TA-repeat in the human ERalpha gene does not correlate with muscle strength or body mass measurements, indicating that body composition is not as sensitive to genetic variation in this receptor as other target organs for estrogen.
  •  
27.
  • Grundberg, Elin, et al. (author)
  • Genetic variation in the human vitamin D receptor is associated with muscle strength, fat mass and body weight in Swedish women
  • 2004
  • In: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 150:3, s. 323-328
  • Journal article (peer-reviewed)abstract
    • Objective: Bone mineral density (BMD) is under strong genetic control and a number of candidategenes have been associated with BMD. Both muscle strength and body weight are considered to beimportant predictors of BMD but far less is known about the genes affecting muscle strength andfat mass. The purpose of this study was to investigate the poly adenosine (A) repeat and the BsmISNP in the vitamin D receptor (VDR) in relation to muscle strength and body composition in healthywomen. Design: A population-based study of 175 healthy women aged 20–39 years was used. Methods: The polymorphic regions in the VDR gene (the poly A repeat and the BsmI SNP) were amplifiedby PCR. Body mass measurements (fat mass, lean mass, body weight and body mass index) andmuscle strength (quadriceps, hamstring and grip strength) were evaluated. Results: Individuals with shorter poly A repeat, ss and/or absence of the linked BsmI restriction site(BB) have higher hamstring strength (ss vs LL, P ¼ 0.02), body weight (ss vs LL, P ¼ 0.049) andfat mass (ss vs LL, P ¼ 0.04) compared with women with a longer poly A repeat (LL) and/or thepresence of the linked BsmI restriction site (bb). Conclusions: Genetic variation in the VDR is correlated with muscle strength, fat mass and bodyweight in premenopausal women. Further functional studies on the poly A microsatellite areneeded to elucidate whether this is the functionally relevant locus or if the polymorphism is in linkagedisequilibrium with a functional variant in a closely situated gene further downstream of the VDR30UTR.
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28.
  • Holleboom, Adriaan G, et al. (author)
  • Heterozygosity for a Loss-of-Function Mutation in GALNT2 Improves Plasma Triglyceride Clearance in Man
  • 2011
  • In: Cell Metabolism. - : Elsevier. - 1550-4131 .- 1932-7420. ; 14:6, s. 811-8
  • Journal article (peer-reviewed)abstract
    • Genome-wide association studies have identified GALNT2 as a candidate gene in lipid metabolism, but it is not known how the encoded enzyme ppGalNAc-T2, which contributes to the initiation of mucin-type O-linked glycosylation, mediates this effect. In two probands with elevated plasma high-density lipoprotein cholesterol and reduced triglycerides, we identified a mutation in GALNT2. It is shown that carriers have improved postprandial triglyceride clearance, which is likely attributable to attenuated glycosylation of apolipoprotein (apo) C-III, as observed in their plasma. This protein inhibits lipoprotein lipase (LPL), which hydrolyses plasma triglycerides. We show that an apoC-III-based peptide is a substrate for ppGalNAc-T2 while its glycosylation by the mutant enzyme is impaired. In addition, neuraminidase treatment of apoC-III which removes the sialic acids from its glycan chain decreases its potential to inhibit LPL. Combined, these data suggest that ppGalNAc-T2 can affect lipid metabolism through apoC-III glycosylation, thereby establishing GALNT2 as a lipid-modifying gene.
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29.
  • Johansson, Peter, 1975-, et al. (author)
  • Development and performance of a sleep estimation algorithm using a single accelerometer placed on the thigh : an evaluation against polysomnography
  • 2023
  • In: Journal of Sleep Research. - : John Wiley & Sons. - 0962-1105 .- 1365-2869. ; 32:2
  • Journal article (peer-reviewed)abstract
    • Accelerometers placed on the thigh provide accurate measures of daily physical activity types, postures and sedentary behaviours, over 24 h and across consecutive days. However, the ability to estimate sleep duration or quality from thigh-worn accelerometers is uncertain and has not been evaluated in comparison with the 'gold-standard' measurement of sleep polysomnography. This study aimed to develop an algorithm for sleep estimation using the raw data from a thigh-worn accelerometer and to evaluate it in comparison with polysomnography. The algorithm was developed and optimised on a dataset consisting of 23 single-night polysomnography recordings, collected in a laboratory, from 15 asymptomatic adults. This optimised algorithm was then applied to a separate evaluation dataset, in which, 71 adult males (mean [SD] age 57 [11] years, height 181 [6] cm, weight 82 [13] kg) wore ambulatory polysomnography equipment and a thigh-worn accelerometer, simultaneously, whilst sleeping at home. Compared with polysomnography, the algorithm had a sensitivity of 0.84 and a specificity of 0.55 when estimating sleep periods. Sleep intervals were underestimated by 21 min (130 min, Limits of Agreement Range [LoAR]). Total sleep time was underestimated by 32 min (233 min LoAR). Our results evaluate the performance of a new algorithm for estimating sleep and outline the limitations. Based on these results, we conclude that a single device can provide estimates of the sleep interval and total sleep time with sufficient accuracy for the measurement of daily physical activity, sedentary behaviour, and sleep, on a group level in free-living settings.
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30.
  • Karlsson, Magnus, et al. (author)
  • Inferior physical performance tests in 10,998 men in the MrOS study is associated with recurrent falls
  • 2012
  • In: Age and Ageing. - : Oxford University Press (OUP). - 0002-0729 .- 1468-2834. ; 41:6, s. 740-746
  • Journal article (peer-reviewed)abstract
    • Background: recurrent fallers are at especially high risk for injuries. Objective: to study whether tests of physical performance are associated with recurrent falls. Subjects: a total of 10,998 men aged 65 years or above. Methods: questionnaires evaluated falls sustained 12 months preceding testing of grip strength, timed stand, 6-m walk and 20-cm narrow walk test. Means with 95% confidence interval (95% CI) are reported. P < 0.01 is a statistically significant difference. Results: in comparison to both occasional fallers and non-fallers, recurrent fallers performed more poorly on all the physical ability tests (all P < 0.001). A score below -2 standard deviations (SDs) in the right-hand grip strength test was associated with an odds ratio of 2.4 (95% CI 1.7, 3.4) for having had recurrent falls compared with having had no fall and of 2.0 (95% CI 1.3, 3.4) for having had recurrent falls compared with having had an occasional fall. Conclusion: low performance in physical ability tests are in elderly men associated with recurrent falls.
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31.
  • Karlsson, Magnus, et al. (author)
  • International and ethnic variability of falls in older men
  • 2014
  • In: Scandinavian journal of public health. - : SAGE Publications. - 1651-1905 .- 1403-4948. ; 42:2, s. 194-200
  • Journal article (peer-reviewed)abstract
    • Aims: Fallers and especially recurrent fallers are at high risk for injuries. The aim of this study was to evaluate fall epidemiology in older men with special attention to the influence of age, ethnicity and country of residence. Methods: 10,998 men aged 65 years or above recruited in Hong Kong, the United States (US) and Sweden were evaluated in a cross-sectional retrospective study design. Self-reported falls and fractures for the preceding 12 months were registered through questionnaires. Group comparisons were done by chi-square test or logistic regression. Results: The proportion of fallers among the total population was 16.5% in ages 65-69, 24.8% in ages 80-84 and 43.2% in ages above 90 (P <0.001). The corresponding proportions of recurrent fallers in the same age groups were 6.3%, 10.1% and 18.2%, respectively (P <0.001), and fallers with fractures 1.0%, 2.3% and 9.1%, respectively (P <0.001). The proportion of fallers was highest in the US, intermediate in Sweden and lowest in Hong Kong (in most age groups P <0.05). The proportion of fallers among white men in the US was higher than in white men in Sweden (all comparable age groups P <0.01) but there were no differences in the proportion of fallers in US men with different ethnicity. Conclusions: The proportion of fallers in older men is different in different countries, and data in this study corroborate with the view that society of residence influences fall prevalence more than ethnicity.
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32.
  • Kilbo Edlund, Karl, et al. (author)
  • Long-term ambient air pollution and coronary atherosclerosis : results from the Swedish SCAPIS study
  • 2024
  • In: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484.
  • Journal article (peer-reviewed)abstract
    • Background and aims: Despite firm evidence for an association between long-term ambient air pollution exposure and cardiovascular morbidity and mortality, results from epidemiological studies on the association between air pollution exposure and atherosclerosis have not been consistent. We investigated associations between long-term low-level air pollution exposure and coronary atherosclerosis.Methods: We performed a cross-sectional analysis in the large Swedish CArdioPulmonary bioImaging Study (SCAPIS, n = 30 154), a random general population sample. Concentrations of total and locally emitted particulate matter <2.5 μm (PM2.5), <10 μm (PM10), and nitrogen oxides (NOx) at the residential address were modelled using high-resolution dispersion models. We estimated associations between air pollution exposures and segment involvement score (SIS), coronary artery calcification score (CACS), number of non-calcified plaques (NCP), and number of significant stenoses, using ordinal regression models extensively adjusted for potential confounders.Results: Median 10-year average PM2.5 exposure was 6.2 μg/m3 (range 3.5–13.4 μg/m3). 51 % of participants were women and 51 % were never-smokers. None of the assessed pollutants were associated with a higher SIS or CACS. Exposure to PM2.5 was associated with NCP (adjusted OR 1.34, 95 % CI 1.13, 1.58, per 2.05 μg/m3). Associations with significant stenoses were inconsistent.Conclusions: In this large, middle-aged general population sample with low exposure levels, air pollution was not associated with measures of total burden of coronary atherosclerosis. However, PM2.5 appeared to be associated with a higher prevalence of non-calcified plaques. The results suggest that increased risk of early-stage atherosclerosis or rupture, but not increased total atherosclerotic burden, may be a pathway for long-term air pollution effects on cardiovascular disease.
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33.
  • Kilbo Edlund, Karl, et al. (author)
  • Long-term ambient air pollution and coronary atherosclerosis: Results from the Swedish SCAPIS study.
  • 2024
  • In: Atherosclerosis. - 1879-1484.
  • Journal article (peer-reviewed)abstract
    • Despite firm evidence for an association between long-term ambient air pollution exposure and cardiovascular morbidity and mortality, results from epidemiological studies on the association between air pollution exposure and atherosclerosis have not been consistent. We investigated associations between long-term low-level air pollution exposure and coronary atherosclerosis.We performed a cross-sectional analysis in the large Swedish CArdioPulmonary bioImaging Study (SCAPIS, n=30154), a random general population sample. Concentrations of total and locally emitted particulate matter <2.5μm (PM2.5), <10μm (PM10), and nitrogen oxides (NOx) at the residential address were modelled using high-resolution dispersion models. We estimated associations between air pollution exposures and segment involvement score (SIS), coronary artery calcification score (CACS), number of non-calcified plaques (NCP), and number of significant stenoses, using ordinal regression models extensively adjusted for potential confounders.Median 10-year average PM2.5 exposure was 6.2μg/m3 (range 3.5-13.4μg/m3). 51% of participants were women and 51% were never-smokers. None of the assessed pollutants were associated with a higher SIS or CACS. Exposure to PM2.5 was associated with NCP (adjusted OR 1.34, 95% CI 1.13, 1.58, per 2.05μg/m3). Associations with significant stenoses were inconsistent.In this large, middle-aged general population sample with low exposure levels, air pollution was not associated with measures of total burden of coronary atherosclerosis. However, PM2.5 appeared to be associated with a higher prevalence of non-calcified plaques. The results suggest that increased risk of early-stage atherosclerosis or rupture, but not increased total atherosclerotic burden, may be a pathway for long-term air pollution effects on cardiovascular disease.
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34.
  • Lindahl, Katarina, et al. (author)
  • Allele Dependent Silencing of Collagen Type I Using Small Interfering RNAs Targeting 3'UTR Indels : a Novel Therapeutic Approach in Osteogenesis Imperfecta
  • 2013
  • In: International Journal of Medical Sciences. - : Ivyspring International Publisher. - 1449-1907. ; 10:10, s. 1333-1343
  • Journal article (peer-reviewed)abstract
    • Osteogenesis imperfecta, also known as "brittle bone disease", is a heterogeneous disorder of connective tissue generally caused by dominant mutations in the genes COL1A1 and COL1A2, encoding the α1 and α2 chains of type I (pro)collagen. Symptomatic patients are usually prescribed bisphosphonates, but this treatment is neither curative nor sufficient. A promising field is gene silencing through RNA interference. In this study small interfering RNAs (siRNAs) were designed to target each allele of 3'UTR insertion/deletion polymorphisms (indels) in COL1A1 (rs3840870) and COL1A2 (rs3917). For both indels, the frequency of heterozygous individuals was determined to be approximately 50% in Swedish cohorts of healthy controls as well as in patients with osteogenesis imperfecta. Cultures of primary human bone derived cells were transfected with siRNAs through magnet-assisted transfection. cDNA from transfected cells was sequenced in order to measure targeted allele/non-targeted allele ratios and the overall degree of silencing was assessed by quantitative PCR. Successful allele dependent silencing was observed, with promising results for siRNAs complementary to both the insertion and non-insertion harboring alleles. In COL1A1 cDNA the indel allele ratios were shifted from 1 to 0.09 and 0.19 for the insertion and non-insertion allele respectively while the equivalent resulting ratios for COL1A2 were 0.05 and 0.01. Reductions in mRNA abundance were also demonstrated; in cells treated with siRNAs targeting the COL1A1 alleles the average COL1A1 mRNA levels were reduced 65% and 78% compared to negative control levels and in cells treated with COL1A2 siRNAs the average COL1A2 mRNA levels were decreased 26% and 49% of those observed in the corresponding negative controls. In conclusion, allele dependent silencing of collagen type I utilizing 3'UTR indels common in the general population constitutes a promising mutation independent therapeutic approach for osteogenesis imperfecta.
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35.
  • Lindahl, Katarina, et al. (author)
  • Genetic epidemiology, prevalence, and genotype-phenotype correlations in the Swedish population with osteogenesis imperfecta
  • 2015
  • In: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 23:8, s. 1042-1050
  • Journal article (peer-reviewed)abstract
    • Osteogenesis imperfecta (OI) is a rare hereditary bone fragility disorder, caused by collagen I mutations in 90% of cases. There are no comprehensive genotype-phenotype studies on 4100 families outside North America, and no population-based studies determining the genetic epidemiology of OI. Here, detailed clinical phenotypes were recorded, and the COL1A1 and COL1A2 genes were analyzed in 164 Swedish OI families (223 individuals). Averages for bone mineral density (BMD), height and yearly fracture rate were calculated and related to OI and mutation type. N-terminal helical mutations in both the alpha 1-and alpha 2-chains were associated with the absence of dentinogenesis imperfecta (P<0.0001 vs 0.0049), while only those in the alpha 1-chain were associated with blue sclera (P = 0.0110). Comparing glycine with serine substitutions, alpha 1-alterations were associated with more severe phenotype (P = 0.0031). Individuals with type I OI caused by qualitative vs quantitative mutations were shorter (P < 0.0001), but did not differ considering fractures or BMD. The children in this cohort were estimated to represent >95% of the complete Swedish pediatric OI population. The prevalence of OI types I, III, and IV was 5.16, 0.89, and 1.35/100 000, respectively (7.40/100 000 overall), corresponding to what has been estimated but not unequivocally proven in any population. Collagen I mutation analysis was performed in the family of 97% of known cases, with causative mutations found in 87%. Qualitative mutations caused 32% of OI type I. The data reported here may be helpful to predict phenotype, and describes for the first time the genetic epidemiology in > 95% of an entire OI population.
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36.
  • Lindahl, Katarina, et al. (author)
  • Genotype-Phenotype Correlations, Response to Bisphosphonate Treatment and Pharmaco-genetics in 150 Swedish Families with Osteogenesis Imperfecta (Type I, IV and III)
  • Other publication (other academic/artistic)abstract
    • Introduction: Osteogenesis imperfecta (OI) is a rare heterogeneous disorder leading to bone fragility, spanning from mild to lethal in severity. Over 1500 mutations have been described in collagen type I, encoded by COL1A1 and COL1A2. Bisphosphonate treatment is standard of care and published studies clearly show beneficial effects on Bone Mineral Density (BMD) and vertebral geometry. However, information on BMD increase in relation to age and BMD at onset is limited and there are few studies on influence of mutation type on treatment response. In this study Swedish patients with OI types I, IV and III were investigated with respect to genotype-phenotype correlations, BMD response on bisphosphonate treatment, and pharmaco-genetics.Materials and Methods: 150 families (202 individuals) with OI participated: 137 type I, 40 type IV and 25 type III. Data on phenotype and bisphosphonate treatment were collected and sequencing of COL1A1 and COL1A2 performed.Results: In 119 families a mutation was detected; in COL1A1 52 quantitative and 35 qualitative mutations were found and in COL1A2 32 qualitative mutations were found. Several unrelated individuals were found to harbor mutations with the same positions and substitutions and only 15 qualitative mutations were novel, supporting the idea of mutational hotspots. Genotype-phenotype analysis confirmed that mutations situated in the a1-chain are associated with a more severe phenotype, blue sclerae are strongly associated with COL1A1 null alleles, qualitative mutations are associated with DI, and for qualitative mutations position relative to N- and C-terminal is correlated to phenotype. A few novel mutations with unconventional locations were found.Bisphosphonate treatment response was inversely correlated with age (p=<0.0001) and lumbar spine BMD at onset (p=0.006). Mutations associated with a more severe phenotype had an improved response to treatment when analyzing 2-year delta lumbar spine Z-score values; mutations in COL1A1 vs. COL1A2 (p=0.03), qualitative mutations in COL1A1 vs. COL1A2 (p=0.006), serine substitutions in COL1A1 vs. COL1A2 (p=0.007) and qualitative vs. qualitative mutations in COL1A1 (p=0.02) all exhibited this pattern. Bisphosphonate response was not correlated to either OI type or gender.Conclusions: The genotype-phenotype correlations described here confirm previous reports of influence of chain affected, intrachain location, and mutation type on phenotype. BMD response to bisphosphonate treatment is inversely related to age and BMD at onset. Pharmaco-genetic analyses show an increased response to bisphosphonate treatment for more severe mutations types. This effect is attenuated over time.
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37.
  • Lindstedt, Sandra, et al. (author)
  • Single-Dose Antibiotic Prophylaxis in Core Prostate Biopsy: Impact of Timing and Identification of Risk Factors.
  • 2006
  • In: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 50:4, s. 832-837
  • Journal article (peer-reviewed)abstract
    • objectives: To assess the level of infectious complications and the impact of timing of a single, prophylactic, oral dose of ciprofloxacin 750 mg given either 2 hours before or in conjunction with ultrasound -guided core biopsy of the prostate in men without recognised risk factors and to analyse potential risk factors. Methods: All men undergoing prostate biopsy for elevated prostate specific antigen or clinical suspected prostate cancer were enrolled in an open, comparative prospective study. Excluded were men with recognised risk factors for infective complications. Two end points were chosen: febrile genitourinary infection and the results of postbiopsy urine culture. Results: A total of 1322 prostate biopsy occasions were made in 1157 men. Twelve (0.9%) cases of febrile genitourinary infections were recorded, two of which had proven sepsis. Administrating the drug 2 hours before or at the time of biopsy (p > 0.5) showed no statistical difference. Eight of 12 patients were shown to have prebiopsy undisclosed risk factors. Four percent developed postbiopsy, asymptomatic, significant bacteriuria. In addition, three (27%) men with prebiopsy unrecognised bacteriuria, who were accidentally enrolled, developed febrile genitourinary infection; one had proven sepsis. Conclusions: A single high-dose of oral ciprofloxacin 750 mg can be administered in direct conjunction with prostate biopsy to men without recognised risk factors, keeping the infection rate at approximately 1%. Bacteriuria before biopsy is a major risk factor for infective complications. Attention given to recognising individual risk factors would reduce the risk of infection further. (c) 2006 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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38.
  • Ljunggren, Anethe, et al. (author)
  • Endurance of Aloneness Among Tibetan Indigenous Women in Western China: Application of Repeat Focus Group Discussions as a Tool for Empowerment and for Data Collection
  • 2009
  • In: Health Care for Women International. - : Informa UK Limited. - 1096-4665 .- 0739-9332. ; 30:9, s. 824-844
  • Journal article (peer-reviewed)abstract
    • In this article we describe Tibetan indigenous women's perceptions and experiences of their own health and life situation in Shichuan Province, China. Fifteen focus group discussions (FGDs) and 10 interviews were conducted. Repeat FGDs were used to empower the women and as a tool to collect data. Content analysis was used to analyze the data, and three subthemes were identified: 'shouldering responsibility in family life,' oenduring reproductive hardship and ill healtho and oreflecting on the future.o The main theme, oexperiencing aloneness,o contained two dimensions: ostrength for surviving under extreme living conditionso and onegative influence on women's endeavor to maintain a healthy behavior.o.
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39.
  • Ljunggren, Mirjam, et al. (author)
  • Association between obstructive sleep apnea and elevated levels of type B natriuretic peptide in a community-based sample of women
  • 2012
  • In: Sleep. - : Oxford University Press (OUP). - 0161-8105 .- 1550-9109. ; 35:11, s. 1521-1527
  • Journal article (peer-reviewed)abstract
    • Study Objectives:Obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular disease. One contributory factor may be hemodynamic stress due to the negative intrathoracic pressure during each episode of apnea. Type B natriuretic peptide (BNP) is secreted by the cardiac ventricles in response to volume expansion and pressure load and the authors hypothesized that there would be an association between indices of OSA during the night and levels of BNP in the morning.Setting:Community-based in Uppsala, Sweden.Participants:There were 349 women who participated.Measurements and Results:Participants underwent full-night polysomnography and anthropometric measurements, and answered questionnaires about medical conditions and current medication. The morning after the polysomnography, blood samples were drawn for analysis of plasma BNP, C-reactive protein, creatinine, and hemoglobin. There was an increase in mean BNP as the severity of sleep apnea increased, increasing from a mean value of 8.5 ng/L among women with an apnea-hypopnea index (AHI) < 5 to 18.0 ng/L in women with an AHI = 30. Elevated BNP levels (= 20 ng/L) were found in 29.8% of the women, whereas 70.2% had normal levels. The odds ratio was 2.2 for elevated BNP levels for women with an AHI of 5-14.9 in relation to women with an AHI < 5, 3.1 for women with an AHI of 15-29.9, and 4.6 for women with an AHI = 30 after adjustment for age, body mass index, systolic blood pressure, antihypertensive drugs, and creatinine.Conclusions:There is a dose-response relationship in women between the severity of sleep apnea during the night and the levels of BNP in the morning.
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40.
  •  
41.
  • Ljunggren, Mirjam, et al. (author)
  • Increased risk of heart failure in women with symptoms of sleep-disordered breathing
  • 2016
  • In: Sleep Medicine. - : Elsevier BV. - 1389-9457 .- 1878-5506. ; 17, s. 32-37
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: An association between obstructive sleep apnea and the incidence of heart failure has been reported in men but not in women. The aim of this study was to investigate whether a combination of snoring and excessive daytime sleepiness, the two main symptoms of obstructive sleep apnea syndrome, was able to predict incident heart failure in a population-based sample of women.METHODS: The population-based cohort study Sleep and Health in Women (SHE; n = 5990 women born between 1901 and 1980) was used, with baseline questionnaire data from April 2000 relating to snoring, excessive daytime sleepiness, and covariates. Using data retrieved from the Swedish National Patient Register and Cause of Death Register, the follow-up of incident heart failure continued until 31 December 2011.RESULTS: Among women with both snoring and excessive daytime sleepiness at baseline, 5.3% developed heart failure during follow-up compared with 0.9% in the reference group with neither snoring nor excessive daytime sleepiness. After adjustment for age, waist circumference, smoking, alcohol, hypertension, diabetes, previous myocardial infarction, physical inactivity, depressive symptoms, menopausal status, and hormone replacement therapy, women with the combination of snoring and excessive daytime sleepiness had a twofold increase in the risk of incident heart failure (hazard ratio [HR] 2.2 95% confidence interval [CI] 1.1-4.4).CONCLUSION: Symptoms of obstructive sleep apnea, that is, the combination of snoring and excessive daytime sleepiness, are associated with an increased risk of developing heart failure in women.
  •  
42.
  • Ljunggren, Mirjam, et al. (author)
  • Obstructive sleep apnea during rapid eye movement sleep is associated with early signs of atherosclerosis in women
  • 2018
  • In: Sleep. - : Oxford University Press. - 0161-8105 .- 1550-9109. ; 41:7
  • Journal article (peer-reviewed)abstract
    • Study Objectives: Although obstructive sleep apnea (OSA) is associated with overall cardiovascular disease and mortality, the association with atherosclerotic cardiovascular disease is less clear, especially in women. Recently, it has been suggested that OSA during rapid eye movement (REM) sleep, associated with long apneas and deep desaturations, could have severe cardiometabolic consequences. The aim of this study was to investigate whether OSA during REM sleep is associated with early signs of atherosclerosis in a population-based sample of women. Methods: In the community-based "Sleep and Health in Women" (SHE) cohort study, 400 women underwent polysomnography, anthropometric measurements, blood sampling, blood pressure measurement, and answered questionnaires. Ten years later, 201 of the original participants, free of known atherosclerotic disease at baseline and without continuous positive airway pressure treatment for OSA, underwent a high-frequency ultrasound of the common carotid artery to assess the individual thickness of the layers of the artery wall. Results: Severe OSA during REM sleep (REM apnea-hypopnea index [AHI] >= 30) was associated with a thicker intima. This association was still significant after adjustment for age, body mass index, alcohol, and smoking, as well as for further adjustment for systolic blood pressure, low-density lipoprotein, C-reactive protein, and diabetes (ss-coefficient, 0.008; p-value, 0.022). The association between a REM AHI of >= 30 and intima thickness was also seen in women with no or mild OSA and normal non-REM AHI. Conclusions: In this study of a community-based sample of women, severe OSA during REM sleep was independently associated with early signs of atherosclerosis. Statement of Significance Individuals with obstructive sleep apnea run an increased risk of cardiovascular disease, but the relationship between obstructive sleep apnea and atherosclerotic diseases is still unclear, especially in women. Sleep apnea and respiration deteriorate during rapid eye movement (REM)-sleep and sleep apnea during REM sleep might have severe adverse effects. In this study of a community-based sample of women, severe sleep apnea during REM sleep was associated with early signs of atherosclerosis, defined as increased intima thickness, at 10 years of follow-up. The association was also seen in women with low overall apnea-hypopnea index, normally not considered for treatment of sleep apnea. This suggests that occurrence of frequent obstructive apneas during REM sleep has to be taken into consideration when diagnosing and treating sleep apnea.
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43.
  • Ljunggren, Mirjam, et al. (author)
  • Rapid eye movement sleep apnea and carotid intima thickness in men and women : a SHE-MUSTACHE cohort study
  • 2022
  • In: Journal of Sleep Research. - : John Wiley & Sons. - 0962-1105 .- 1365-2869. ; 31:5
  • Journal article (peer-reviewed)abstract
    • Rapid eye movement (REM) obstructive sleep apnea might be particularly harmful to the cardiovascular system. We aimed to investigate the association between sleep apnea during REM sleep and signs of atherosclerotic disease in the form of carotid intima thickness in a community-based sample of men and women and possible sex differences in this association. The association between sleep apnea during REM sleep and intima thickness was analysed cross-sectionally in women from the community-based "Sleep and Health in Women" (SHE) study (n = 253) and age- and body mass index (BMI)-matched men from the "Men in Uppsala; a Study of sleep, Apnea and Cardiometabolic Health" (MUSTACHE) study (n = 338). Confounders adjusted for were age, BMI, gender, alcohol, and smoking. All participants underwent a full-night polysomnography, high-resolution ultrasonography of the common carotid artery, anthropometric measurements, blood pressure measurements, and answered questionnaires. There was an association between sleep apnea during REM sleep and thicker carotid intima that remained after adjustment for confounding (adjusted β = 0.008, p = 0.032). The intima was increased by 9.9% in the group with severe sleep apnea during REM sleep, and this association between severe sleep apnea during REM sleep and increased intima thickness remained after adjustment for confounders (adjusted β = 0.043, p = 0.021). More women than men had severe sleep apnea during REM sleep; moreover, in sex-stratified analyses, the association between sleep apnea during REM sleep and intima thickness was found in women but not in men. We conclude that severe REM sleep apnea is independently associated with signs of atherosclerosis. When stratified by sex, the association is seen in women but not in men.
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44.
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45.
  • Ljunggren Ribom, Eva, 1966- (author)
  • Muscles, Estrogen, and Bone
  • 2003
  • Doctoral thesis (other academic/artistic)abstract
    • Sweden has one of the highest incidences of osteoporotic fractures in the world. A more sedentary lifestyle is one of several proposed reasons for the increase in osteoporosis seen in the developed countries. The aim of this thesis was primarily to study the influence of muscle strength, and body composition, on bone mineral density, BMD, in young adults. The second aim was to evaluate the possible influence of estrogen on muscle strength in women.A population-based study of 113 subjects (53 men and 60 women) aged 22-85 showed associations for premenopausal, but not postmenopausal women, between isometric quadriceps muscle strength and BMD in the total body, lumbar spine, and femoral neck. In men there was only an association between muscle strength and BMD in the total body. Another population-based study of 125 randomly selected young adults (64 women and 61 men) showed that total body BMD, TBMD, is influenced by isokinetic knee flexion and extension strength in women but not in men where body composition influenced TBMD. In 159 randomly selected young adult women (20-39 years) knee flexion and extension strength influenced not only TBMD but also total hip BMD, and heel BMD. However, lean body mass and body weight were better predictors for BMD at these skeletal sites. An extension of this study involving 335 women again demonstrated that lean body mass is the best predictor of BMD. This study also showed that Uppsala women aged 20-39 years have a BMD that is approximately 0.1-1.2 SD (2-12 %) above international/national references. In addition marked variations in BMD T-scores between various skeletal sites were noted. In Conclusion: The association between muscle strength and BMD is evident in women in their early twenties but with age lean body mass and body weight becomes better predictors for BMD. In men lean body mass and body composition but not muscle strength predicted BMD. Hormone replacement therapy does not influence muscle strength and there is no association between allelic variations in the estrogen receptor alpha and muscle strength in women.
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46.
  • Ljunggren, Stefan, et al. (author)
  • Biomonitoring of Metal Exposure During Additive Manufacturing (3D Printing)
  • 2019
  • In: SH@W Safety and Health at Work. - : Elsevier. - 2093-7911 .- 2093-7997. ; 10:4, s. 518-526
  • Journal article (peer-reviewed)abstract
    • Background: Additive manufacturing (AM) is a rapidly expanding new technology involving challenges to occupational health. Here, metal exposure in an AM facility with large-scale metallic component production was investigated during two consecutive years with preventive actions in between.Methods: Gravimetric analyzes measured airborne particle concentrations, and filters were analyzed for metal content. In addition, concentrations of airborne particles <300 nm were investigated. Particles from recycled powder were characterized. Biomonitoring of urine and dermal contamination among AM operators, office personnel, and welders was performed.Results: Total and inhalable dust levels were almost all below occupational exposure limits, but inductively coupled plasma mass spectrometry showed that AM operators had a significant increase in cobalt exposure compared with welders. Airborne particle concentrations (<300 nm) showed transient peaks in the AM facility but were lower than those of the welding facility. Particle characterization of recycled powder showed fragmentation and condensates enriched in volatile metals. Biomonitoring showed a nonsignificant increase in the level of metals in urine in AM operators. Dermal cobalt and a trend for increasing urine metals during Workweek Year 1, but not in Year 2, indicated reduced exposure after preventive actions.Conclusion: Gravimetric analyses showed low total and inhalable dust exposure in AM operators. However, transient emission of smaller particles constitutes exposure risks. Preventive actions implemented by the company reduced the workers' metal exposure despite unchanged emissions of particles, indicating a need for careful design and regulation of the AM environments. It also emphasizes the need for relevant exposure markers and biomonitoring of health risks.
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47.
  • Mossberg, Anki, et al. (author)
  • Bladder cancers respond to intravesical instillation of HAMLET (human alpha-lactalbumin made lethal to tumor cells).
  • 2007
  • In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 121:6, s. 1352-1359
  • Journal article (peer-reviewed)abstract
    • We studied if bladder cancers respond to HAMLET (human alpha-lactalburnin made lethal to tumor cells) to establish if intravesical HAMLET application might be used to selectively remove cancer cells in vivo. Patients with nonmuscle invasive transitional cell carcinomas were included. Nine patients received 5 daily intravesical instillations of HAMLET (25 mg/ml) during the week before scheduled surgery. HAMLET stimulated a rapid increase in the shedding of tumor cells into the urine, daily, during the 5 days of instillation. The effect was specific for HAMLET, as intravesical instillation of NaCl, PBS or native a-lactalbumin did not increase cell shedding. Most of the shed cells were dead and an apoptotic response was detected in 6 of 9 patients, using the TUNEL assay. At surgery, morphological changes in the exophytic tumors were documented by endoscopic photography and a reduction in tumor size or change in tumor character was detected in 8 of 9 patients. TUNEL staining was positive in biopsies from the remaining tumor in 4 patients but adjacent healthy tissue showed no evidence of apoptosis and no toxic response. The results suggest that HAMLET exerts a direct and selective effect on bladder cancer tissue in vivo and that local HAMLET administration might be of value in the future treatment of bladder cancers. (c) 2007 Wiley-Liss, Inc.
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48.
  • Ohlsson, Lars, et al. (author)
  • Increased level of circulating cell-free mitochondrial DNA due to a single bout of strenuous physical exercise
  • 2020
  • In: European Journal of Applied Physiology. - : Springer. - 1439-6319 .- 1439-6327. ; 120, s. 897-905
  • Journal article (peer-reviewed)abstract
    • Purpose Physical exercise is reported to affect the immune response in various ways. Thus, the levels of pro-inflammatory cytokines as well as the abundance of circulating leukocytes are changed. In this study, the occurence of circulating cell-free mitochondrial DNA (cfmtDNA) and nuclear DNA (nDNA) was investigated in connection with a single bout of strenuous physical exercise. Methods Healthy volunteers performed a controlled ergo-spirometry cycle test and venous blood samples were taken at different time-points to analyze the concentration of blood components before, during and after the test. The number of circulating leukocytes was measured, as well as secretion of the soluble urokinase activator receptor (suPAR). Results Cf-mtDNA significantly increased during exercise, compared to baseline values and after 30 and 90 min of rest. Circulating leukocytes increased during exercise, but returned to baseline levels afterwards. Surface expression of the urokinase plasminogen activating receptor (uPAR) on neutrophils decreased significantly during exercise. The concentration of suPAR tended to increase during exercise but only significantly after 90 min of rest. Conclusion Increased concentration of cf-mtDNA indicates that cell damage takes place during high intensity training. Hypoxia and tissue damage are likely causes of cf-mtDNA from muscle cells. The levels of cf-mtDNA remain high during the initial rest, due to the decreasing numbers of leukocytes normally clearing the plasma from cf-mtDNA. The increased levels of suPAR further emphasize that strenuous physical exercise causes a reaction similar to inflammation. Further studies are needed to detect the source of increased cf-mtDNA and the corresponding increase of suPAR liberation.
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49.
  • Ohlsson, Lars, et al. (author)
  • Leaky gut biomarkers in depression and suicidal behavior
  • 2019
  • In: Acta Psychiatrica Scandinavica. - : Wiley. - 0001-690X .- 1600-0447. ; 139:2, s. 185-193
  • Journal article (peer-reviewed)abstract
    • Objective: Inflammation is associated with major depressive disorder (MDD) and suicidal behavior. According to the ‘leaky gut hypothesis’, increased intestinal permeability may contribute to this relationship via bacterial translocation across enterocytes. We measured plasma levels of gut permeability markers, in patients with a recent suicide attempt (rSA), MDD subjects with no history of a suicide attempt (nsMDD), and healthy controls (HC), and related these markers to symptom severity and inflammation. Method: We enrolled rSA (n = 54), nsMDD (n = 13), and HC (n = 17). Zonulin, intestinal fatty acid binding protein (I-FABP), soluble CD14, and interleukin-6 (IL-6) were quantified in plasma. Montgomery–Åsberg Depression Rating Scale (MADRS) and Suicide Assessment Scale (SUAS) were used for symptom assessments. Results: The rSA group displayed higher I-FABP and lower zonulin levels compared with both the nsMDD and the HC groups (all P < 0.001). IL-6 correlated positively with I-FABP (r = 0.24, P < 0.05) and negatively with zonulin (r = −0.25, P < 0.05). In all subjects, I-FABP levels correlated positively with MADRS (r = 0.25, P < 0.05) and SUAS scores (r = 0.38, P < 0.001), and the latter correlation was significant also in the nsMDD group (r = 0.60, P < 0.05). Conclusion: The ‘leaky gut hypothesis’ may improve our understanding of the link between inflammation and suicidal behavior. These findings should be considered preliminary until replicated in larger cohorts.
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50.
  • Olsson, Jenny, et al. (author)
  • Pre-medical assessment of root canal-filled teeth with asymptomatic apical periodontitis : a multifaceted balancing act
  • 2023
  • In: International Endodontic Journal. - : John Wiley & Sons. - 0143-2885 .- 1365-2591. ; 56:9, s. 1063-1076
  • Journal article (peer-reviewed)abstract
    • AIM: Prior to certain medical therapies, dental assessment and treatment of oral foci of infection are recommended. The aim of the present study was to acquire a deeper understanding of the decision-making process regarding pre-medical management of root canal-filled teeth with asymptomatic apical periodontitis.METHODOLOGY: Hospital-affiliated dentists in Sweden were contacted for a semi-structured, in-depth interview. The absolute inclusion criterion was that the dentists had experienced and could recount at least two authentic cases involving root canal-filled teeth with asymptomatic apical periodontitis - one case having resulted in pre-medical treatment, and one having resulted in expectancy. Fourteen interviews, with fourteen informants, were conducted and included in the study. During the interviews, open-ended questions and comments encouraging the informants to elaborate and clarify their experiences were offered. The interviews were digitally recorded, transcribed verbatim and analyzed using Qualitative Content Analysis with an inductive approach.RESULTS: A theme describing the latent content was identified through interpretation of the collected data: A multifaceted balancing act characterized by a sometimes-difficult risk-benefit-estimation, where an increased uncertainty entails an increased reliance on external opinions. Three main categories, comprising four subcategories, describing the manifest content were recognized: The tipping scale, The team effort and The frame of reference.CONCLUSION: The current interview study found pre-medical decision-making regarding root canal-filled teeth with asymptomatic apical periodontitis to be a multifactorial and contextual process marked by uncertainty and collaborative measures. Further research, resulting in the development of evidence-based treatment guidelines, is suggested necessary.
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