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  • 251.
    Leander, Mai
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Lampa, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Janson, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Lungmedicin och allergologi.
    Svärdsudd, Kurt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och klinisk epidemiologi.
    Uddenfeldt, Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Rask-Andersen, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Determinants for a low health-related quality of life in asthmatics2012Ingår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 117, nr 1, s. 57-66Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    People with asthma suffer from impaired health-related quality of life (HRQL) but the determinants of HRQL among asthmatics are not completely understood. The aim of this study was to study determinants of low HRQL in asthmatics and to study whether the determinants of HRQL differ between sexes and age groups.

    A cohort of three age groups in Sweden was investigated in 1990 using a respiratory questionnaire. To study quality of life, the generic instrument Gothenburg Quality of Life was used. The participants were also investigated with interviews, spirometry and allergy testing. Asthma was diagnosed in 616 subjects.

    Fifty-eight percent (n=359) of the subjects were women. Twenty-four percent were smokers, 22% ex-smokers and 54% were non-smokers. Women were more likely than men to report poor health-related quality of life. Respiratory symptoms severity was another independent determinant of a lower quality of life as well as airway responsiveness to irritants. Current and former smokers also reported lower quality of life. Finally, absenteeism from school and work was associated with lower quality of life.

    Factors such as sex, smoking habits, airway responsiveness to irritants, respiratory symptom severity, allergy, and absenteeism from school and work were associated with low HRQL in asthmatics.

  • 252.
    Leander, Mai
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Lungmedicin och allergologi.
    Lampa, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Rask-Andersen, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Franklin, Karl
    Gislason, Thorarinn
    Oudin, Anna
    Svanes, Cecilie
    Toren, Kjell
    Janson, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Lungmedicin och allergologi.
    Impact of anxiety and depression on respiratory symptoms2014Ingår i: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 108, nr 11, s. 1594-1600Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Psychological factors such as anxiety and depression are prevalent in patients with asthma. The purpose of this study was to investigate the relationship between respiratory symptoms and psychological status and to estimate the importance of psychological status in comparison with other factors that are known to be associated with respiratory symptoms. This study included 2270 subjects aged 20-44 (52% female) from Sweden, Iceland, and Norway. Each participant underwent a clinical interview including questions on respiratory symptoms. Spirometry and methacholine challenge were performed. Symptoms of depression and anxiety were measured using the Hospital Anxiety and Depression Scale (HADS). Eighty-two percent of the subjects reported no anxiety or depression whatsoever, 11% reported anxiety, 2.5% depression and 4% reported both anxiety and depression. All respiratory symptoms, such as wheezing, breathlessness and nightly symptoms, were more common, at a statistically significant level, in participants who had depression and anxiety, even after adjusting for confounders (ORs 1.33-1.94). The HADS score was the most important determinant for nightly symptoms and attacks of breathlessness when at rest whereas bronchial responsiveness was the most important determinant for wheezing, and breathlessness when wheezing. The probability of respiratory symptoms related to HADS score increased with increasing HADS score for all respiratory symptoms. In conclusion, there is a strong association between respiratory symptoms and psychological status. There is therefore a need for interventional studies designed to improve depression and anxiety in patients with respiratory symptoms.

  • 253. Lee, Duk-Hee
    et al.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Jacobs, David R., Jr.
    Salihovic, Samira
    van Bavel, Bert
    Lind, Monica P.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Does Mortality Risk of Cigarette Smoking Depend on Serum Concentrations of Persistent Organic Pollutants?: Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) Study2014Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 5, s. e95937-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cigarette smoking is an important cause of preventable death globally, but associations between smoking and mortality vary substantially across country and calendar time. Although methodological biases have been discussed, it is biologically plausible that persistent organic pollutants (POPs) like polychlorinated biphenyls (PCBs) and organochlorine (OC) pesticides can affect this association. This study was performed to evaluate if associations of cigarette smoking with mortality were modified by serum concentrations of PCBs and OC pesticides. We evaluated cigarette smoking in 111 total deaths among 986 men and women aged 70 years in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) with mean follow-up for 7.7 years. The association between cigarette smoking and total mortality depended on serum concentration of PCBs and OC pesticides (P value for interaction = 0.02). Among participants in the highest tertile of the serum POPs summary score, former and current smokers had 3.7 (95% CI, 1.5-9.3) and 6.4 (95% CI, 2.3-17.7) times higher mortality hazard, respectively, than never smokers. In contrast, the association between cigarette smoking and total mortality among participants in the lowest tertile of the serum POPs summary score was much weaker and statistically nonsignificant. The strong smoking-mortality association observed among elderly people with high POPs was mainly driven by low risk of mortality among never smokers with high POPs. As smoking is increasing in many low-income and middle-income countries and POPs contamination is a continuing problem in these areas, the interactions between these two important health-related issues should be considered in future research.

  • 254. Lee, Duk-Hee
    et al.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Jacobs, David R
    Salihovic, Samira
    van Bavel, Bert
    Lind, Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Associations of persistent organic pollutants with abdominal obesity in the elderly: The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study2012Ingår i: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 40, s. 170-178Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: In animal experiments, persistent organic pollutants (POPs) have induced visceral obesity. To address this possibility in humans, we evaluated associations between POPs and abdominal obesity both cross-sectionally and prospectively.

    METHODS: Twenty-one plasma POPs (16 polychlorinated biphenyl (PCB) congeners, 3 organochlorine (OC) pesticides, 1 brominated diphenyl ether (BDE), and 1 dioxin) were measured at baseline in 970 participants aged 70years of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), with prospective analyses in 511 participants re-examined after 5years. Abdominal obesity was defined by an increased waist circumference.

    RESULTS: In the cross-sectional analyses, concentrations of the less chlorinated PCBs, OC pesticides such as p,p'-DDE and dioxin had adjusted odds ratios of 2 to 3 for abdominal obesity. Many relations had inverted U-shapes rather than being linear, particularly in women. In contrast, concentrations of highly chlorinated PCBs were strongly inversely associated with abdominal obesity. In a single model including summary measures of the less chlorinated PCBs, highly chlorinated PCBs, and OC pesticides, both the positive associations and inverse associations strengthened. Similar but somewhat weaker associations were seen between POPs and risk of development of abdominal obesity in the prospective analyses.

    CONCLUSION: Using both a cross-sectional and a prospective design, low-dose exposure to less chlorinated PCBs, p,p'-DDE, and dioxin, were associated with existence or development of abdominal obesity, while highly chlorinated PCBs had an opposite association in an elderly population, despite the previous observation of higher incident diabetes associated with these same PCBs.

  • 255. Lee, Duk-Hee
    et al.
    Lind, Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Jacobs, David R
    Salihovic, Samira
    van Bavel, Bert
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Polychlorinated biphenyls and organochlorine pesticides in plasma predict development of type 2 diabetes in the elderly: the prospective investigation of the vasculature in Uppsala Seniors (PIVUS) study2011Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 34, nr 8, s. 1778-1784Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Persistent organic pollutants (POPs), lipophilic chemicals that accumulate mainly in adipose tissue, have recently been linked to type 2 diabetes. However, evidence from prospective studies is sparse. This study was performed to evaluate prospective associations of type 2 diabetes with selected POPs among the elderly.

    RESEARCH DESIGN AND METHODS: Nineteen POPs (14 polychlorinated biphenyl [PCB] congeners, 3 organochlorine pesticides, 1 brominated diphenyl ether, and 1 dioxin) were measured in plasma collected at baseline in 725 participants, aged 70 years, of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS).

    RESULTS: After adjusting for known type 2 diabetes risk factors, including obesity, odds ratios (ORs) (95% CIs) for type 2 diabetes at age 75 years (n = 36) according to the quintiles of a summary measure of concentrations of PCBs (vs. the lowest quintile) were 4.5, 5.1, 8.8 (1.8-42.7), and 7.5 (1.4-38.8) (P(trend) <0.01). Among organochlorine pesticides, adjusted ORs across concentrations of trans-nonachlor showed that P(trend) = 0.03. Adjusted ORs (95% CIs) across quintiles of the sum of three organochlorine pesticides were 1.1, 1.6, 1.5, and 3.4 (1.0-11.7) (P(trend) = 0.03). Neither brominated diphenyl ether 47 nor dioxin was significantly associated with incident diabetes. The sum of PCBs improved reclassification significantly when added to traditional risk factors for diabetes.

    CONCLUSIONS: Despite the small number of incident cases, this study found that environmental exposure to some POPs substantially increased risk of future type 2 diabetes in an elderly population.

  • 256.
    Lee, Duk-Hee
    et al.
    Kyungpook Natl Univ, Sch Med, Dept Prevent Med, Daegu, South Korea.;Kyungpook Natl Univ, Dept Biomed Sci, Plus KNU Biomed Convergence Program BK21, Daegu, South Korea..
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Jacobs, David R., Jr.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA..
    Salihovic, Samira
    Univ Orebro, Sch Sci & Technol, MTM Res Ctr, SE-70182 Orebro, Sweden..
    van Bavel, Bert
    Univ Orebro, Sch Sci & Technol, MTM Res Ctr, SE-70182 Orebro, Sweden..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Association between background exposure to organochlorine pesticides and the risk of cognitive impairment: A prospective study that accounts for weight change2016Ingår i: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 89-90, s. 179-184Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Background exposure to organochlorine (OC) pesticides was recently linked to cognitive impairment and dementia in cross-sectional and case-control studies. This prospective study was performed to evaluate if OC pesticides at baseline are associated with the future risk of cognitive impairment in elderly, with particular focus on weight change. Methods: Plasma concentrations of 3 OC pesticides (p,p'-DDE, trans-nonachlor, and hexachlorobenzene) were measured among 989 men and women aged 70 years in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). Cognitive impairment was validated by reviewing medical records. During the ten year follow-up, cognitive impairment was developed in 75 subjects. When weight change from age 70 to 75 was considered in analyses, elderly with incident cases before age 75 were excluded to keep the prospective perspective, leaving 795 study subjects and 44 incident cases. Results: The summary measure of 3 OC pesticides predicted the development of cognitive impairment after adjusting for covariates, including weight change. Compared to subjects with OC pesticides <25th percentile, adjusted hazard ratios (HRs) in those with 25th-<75th and >= 75th percentiles were 3.5 (95% confidence interval: 1.5-8.5) and 3.2 (1.1-7.6), respectively (P-trend = 0.04). Among 506 subjects who maintained or gained body weight, adjusted HRs were 6.9 and 11.6 (1.4-92.6) among the elderly in the 25th-<75th and >= 75th percentiles compared to <25th percentile (P-trend < 0.01). Conclusions: This prospective study demonstrates that background exposure to OC pesticides are linked to the risk of developing cognitive impairment in elderly. The role of the chronic exposure to low dose OC pesticides in the development of dementia should be further evaluated in other populations.

  • 257. Lee, Duk-Hee
    et al.
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Jacobs, David R., Jr.
    Salihovic, Samira
    van Bavel, Bert
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Background exposure to persistent organic pollutants predicts stroke in the elderly2012Ingår i: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 47, s. 115-120Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background exposure to persistent organic pollutants (POPs), lipophilic xenobiotics that accumulate mainly in adipose tissue, has recently emerged as a new risk factor for cardiovascular diseases. This prospective study was performed to evaluate if plasma concentrations of selected POPs predict incident stroke among the elderly. Twenty-one POPs (including 16 polychlorinated biphenyl (PCB) congeners, 3 organochlorine (OC) pesticides, 1 brominated diphenyl ether (BDE), and 1 dioxin) were measured in plasma collected at baseline in 898 participants aged 70 years of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). Stroke diagnosis was validated by hospital records. During the five year follow-up, 35 subjects developed hospital-treated stroke. After adjusting for known stroke risk factors, most PCBs with 4, 5, or 6 chlorine atoms, p,p'-DDE, trans-nonachlor, and octachlorodibenzo-p-dioxin significantly predicted the risk of stroke. Across quartiles of summary measures of PCBs and OC pesticides, the adjusted ORs were 1.0, 0.8 (95% confidence interval: 0.2-2.5), 1.2 (0.4-3.4), and 2.1 (0.7-6.2) for PCBs and 1.0, 1.2 (0.3-4.2), 2.3 (0.7-6.9), and 3.0 (1.0-9.4) for OC pesticides (P for trend = 0.11 and 0.03, respectively). The adjusted ORs among participants >= 90th percentile of the summary measures were 5.5 (1.7-18.1) for PCBs and 4.0 (1.1-14.6) for OC pesticides; corresponding ORs for those >= 95th percentile were 7.8 (2.1-29.6) and 9.5 (2.3-38.9). Background exposure to POPs may play an important role in development or progression of stroke in the elderly.

  • 258. Lee, Duk-Hee
    et al.
    Porta, M
    Lind, L
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Jacobs, D
    Neurotoxic chemicals in adipose tissue: a role in puzzling findings on obesity and dementia.Ingår i: NeurologyArtikel i tidskrift (Refereegranskat)
  • 259.
    Lee, Duk-Hee
    et al.
    Kyungpook Natl Univ, Sch Med, Dept Prevent Med, Daegu, South Korea.
    Porta, Miquel
    Univ Autonoma Barcelona, Sch Med, Hosp del Mar, Inst Med Res IMIM, Barcelona, Spain.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Jacobs, David R
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
    Neurotoxic chemicals in adipose tissue: A role in puzzling findings on obesity and dementia2018Ingår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 90, nr 4, s. 176-182Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Midlife obesity is associated with increased risk of dementia, whereas late-life obesity is commonly associated with a lower risk of dementia. Although methodologic issues are often discussed in this apparent risk reversal, chronic exposure to low-dose organochlorine pesticides (OCPs), an emerging risk factor for dementia in general populations, may contribute to a direct explanation for these differences. OCPs are strong lipophilic chemicals with very long half-lives (several years), primarily stored in adipose tissue and very slowly released and metabolized over years. As serum concentrations of neurotoxic OCPs strongly correlate with brain OCPs (r = 0.95), any condition enhancing the release of OCPs from the adipose tissue into circulation would increase the risk of dementia. Increased release of OCPs from adipose tissue typically occurs in (1) dysfunctional adipocytes accompanied by uncontrolled lipolysis and (2) weight loss. Weight gain may help sequester circulating OCPs in adipose tissue. As obesity is the most common reason that adipocytes become dysfunctional, midlife obesity can increase dementia risk through the chronic release of OCPs into circulation. However, late-life obesity potentially decreases dementia risk because weight loss after midlife will increase the release of OCPs while weight gain may actually decrease the release. These countervailing forces may underlie paradoxical associations with dementia of obesity in midlife vs late life which is influenced by weight change after midlife. This hypothesis should be tested in future experimental and human studies on obesity and dementia.

  • 260. Leijon, O.
    et al.
    Lindahl, Erica
    Uppsala universitet, Enheter med anknytning till universitetet, Institutet för arbetsmarknadspolitisk utvärdering (IFAU).
    Toren, K.
    Vingård, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Josephson, Malin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    First-time decisions regarding work injury annuity due to occupational disease: a gender perspective2014Ingår i: Occupational and Environmental Medicine, ISSN 1351-0711, E-ISSN 1470-7926, Vol. 71, nr 2, s. 147-153Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives This study presents an investigation of first-time decisions regarding work injury annuity due to occupational disease. Focus is a number of potential underlying factors behind the gender gap, where women are disadvantaged, in the granting of work injury annuity. Methods All 99 subjects (80 men and 19 women) who met the conditions of long-lasting reduction of work ability due to occupational disease (not occupational accident) in the Swedish Work Injury Insurance Act and were granted work injury annuity in 2010, together with a random sample of 118 subjects (55 men and 63 women) who were denied annuity in the same year, were selected for analysis. Each subject's case file from the Social Insurance Agency was examined with regards to cause of disease, diagnosis and the Social Insurance Agency's management and decision making of claims. The data were analysed by logistic regression analysis. Results Men had a higher probability of being granted work injury annuity than women for musculoskeletal disorders (OR 4.16), mental disorders (OR 7.93) and diseases in other diagnostic chapters (OR 3.65). After adjustment for age, country of birth, diagnosis, work exposure factors and decision support factors, the higher probability for men of being granted work injury annuity remained (full model: OR 2.67, 95% Cl 1.20 to 5.94). Conclusions Actions are necessary in order to establish equitable and gender-neutral treatment of work injury insurance claims. There is a need for more detailed knowledge of exposures in female-dominated jobs and the relationship between these exposures and occupational disease.

  • 261. Leijon, Ola
    et al.
    Josephson, Malin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Osterlund, Niklas
    How common is change of primary diagnosis during an episode of sickness benefit?: A register study of medical sickness certificates issued 2010-2012 in Sweden2015Ingår i: Scandinavian Journal of Public Health, ISSN 1403-4948, E-ISSN 1651-1905, Vol. 43, nr 1, s. 44-51Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim: The aims of this study were to investigate how common it is to change primary diagnosis between different diagnostic chapters during a sick-leave spell, and to explore patterns of diagnostic changes. Methods: The unit for analysis was episode of sickness benefit, that is, sick leave >14 days, which commenced between 2010 and 2012 in Sweden. For each case, the primary diagnosis was retrieved from the first and last/latest medical sickness certificate, respectively. The number of days of sickness benefit was linked to the cases. Any change of primary diagnosis was analysed by diagnostic chapter according to the ICD-10, and this was done separately for women and men. Results: In total, 803,041 cases of sickness benefit (63% women) were included in the study. During a sick-leave spell, 7.1% of female cases and 6.6% of male cases changed their primary diagnosis to a diagnosis from another diagnostic chapter. The change of primary diagnosis increased with the number of days with sickness benefit. For female cases, this increase was from 2.0% for cases that lasted 15-30 days to 20.2% for cases that lasted >365 days. For male cases, the corresponding increase was from 1.8% to 21.2%. A change of primary diagnosis was least common among those initially sick-listed for mental disorders and musculoskeletal disorders. The patterns of diagnostic changes were rather similar for women and men. Conclusions: A change of diagnosis during a sick-leave spell needs to be taken into consideration by the sickness insurance system and in the actions taken by its administration. Registry-based studies of sickness insurance need to consider diagnostic changes in both the study design and the interpretation of results.

  • 262. Leijon, Ola
    et al.
    Josephson, Malin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Osterlund, Niklas
    Sick-listing adherence: a register study of 1.4 million episodes of sickness benefit 2010-2013 in Sweden2015Ingår i: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 15, artikel-id 380Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: This register study aims to increase the knowledge on how common it is that sickness benefit recipients are sick-listed for as long as their physician prescribes in their medical sickness certificate, i.e. sick-listing adherence, or wholly/partly bring return-to-work (RTW) forward, i.e. early RTW. Methods: The unit for analysis was an episode of 100% sickness benefit, commenced between 1 January 2010 and 31 December 2013. Completed episodes of sickness benefit and full or partial early RTW was analysed by comparing the prescribed length of sick leave in medical sickness certificates and benefit days disbursed by the sickness insurance system. Probability for a full and partial early RTW was estimated with hazard ratio (HR) using the Cox proportional hazard model. Results: In total, about 1.4 million episodes of sickness benefit (60% women) were included in the study. The overall sick-listing adherence was 84% for women and 82% for men during the first year of sick leave. Adherence varied between 82 and 87% among women and between 79 and 86% among men with regard to ICD-10 diagnosis chapter. The probability of an early RTW varied between diagnosis chapters, where mental disorders was associated with a lower probability of a full early RTW among women and men (HR 0.52 and HR 0.47) as well as a partial early RTW (HR 0.51 and HR 0.46). Younger age (16-29 years), high educational level and high income was associated with a higher probability of an early RTW, while older age (>= 50 years), not native-born, low educational level, unemployment and parental leave were associated with a lower probability. Conclusion: The study demonstrates that sick-listing adherence is relatively high. Probability of an early RTW differs with regard to diagnosis chapter, demographic, socioeconomic and labour market characteristics of the sickness benefit recipients. Interventions intended to improve the sick-listing process, and to affect the length and degree of sick leave in certain target groups, should include measures targeted at physicians' sick-listing practices. Policies and economic incentives aimed at promoting RTW need to focus on individuals' residual capacity for work.

  • 263. Leijon, Ola
    et al.
    Lindberg, Per
    Josephson, Malin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Wiktorin, Christina
    Different working and living conditions and their associations with persistent neck/shoulder and/or low back disorders2007Ingår i: Occupational and Environmental Medicine, ISSN 1351-0711, E-ISSN 1470-7926, Vol. 64, nr 2, s. 115-121Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: To investigate whether different combinations of working and living conditions are associated with the risk for persistent neck/shoulder and/or low back disorders. The underlying purpose of this contextual approach was to identify target groups for primary/secondary prevention. Methods: In a baseline study, 11 groups with different working and living conditions were identified by cluster analysis. In this study, these 11 groups were followed up by a postal questionnaire 5 years after baseline (response rate 82%, n=1095). Results: Five of the groups-the onerous human services job, the free agent, the family burden, the mentally stretched and the physically strained groups-had an increased risk for persistent disorders (OR 2.38-2.70). Four of these groups had rather sex-specific working and living conditions. Conclusions: The results support the hypothesis that different combinations of working and living conditions may increase the risk for persistent neck/shoulder and/or low back disorders to different degrees. Sex-specific working and living conditions increased the risk for women as well as for men, irrespective of whether the conditions were specific to women or men.

  • 264. Leineweber, Constanze
    et al.
    Westerlund, Hugo
    Theorell, Töres
    Kivimäki, Mika
    Westerholm, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Alfredsson, Lars
    Covert coping with unfair treatment at work and risk of incident myocardial infarction and cardiac death among men: Prospective cohort study2011Ingår i: Journal of Epidemiology and Community Health, ISSN 0143-005X, E-ISSN 1470-2738, Vol. 65, nr 5, s. 420-425Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Covert coping with unfair treatment at work-occurring when an employee does not show the "aggressor" that he/she feels unfairly treated-has been found to be associated with cardiovascular risk factors. This study examined whether covert coping also predicts incident coronary heart disease.

    Methods A prospective cohort study (the WOLF Stockholm study) of workplaces in the Stockholm area, Sweden. The participants were 2755 men with no history of myocardial infarction at baseline screening in 1992-1995. The main outcome measure was hospitalisation due to myocardial infarction or death from ischaemic heart disease until 2003 obtained from national registers (mean follow-up 9.8 +/- 0.9 years).

    Results Forty-seven participants had myocardial infarction or died from ischaemic heart disease during follow-up. After adjustment for age, socioeconomic factors, risk behaviours, job strain and biological risk factors at baseline, there was a dose-response relationship between covert coping and risk of incident myocardial infarction or cardiac death (p for trend=0.10). Men who frequently used covert coping had a 2.29 (95% CI 1.00 to 5.29) times higher risk than those who did not use coping. Restricting the analysis to direct coping behaviours only strengthened this association (p for trend=0.02).

    Conclusions In this study, covert coping is strongly related to increased risk of hard-endpoint cardiovascular disease.

  • 265.
    Lejonklou, Margareta H.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Christiansen, S.
    Tech Univ Denmark, Div Diet Dis Prevent & Toxicol, Morkhoj Bygade 19, DK-2860 Soborg, Denmark..
    Örberg, Jan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Shen, Ling
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Larsson, Sune
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Boberg, J.
    Tech Univ Denmark, Div Diet Dis Prevent & Toxicol, Morkhoj Bygade 19, DK-2860 Soborg, Denmark..
    Hass, U.
    Tech Univ Denmark, Div Diet Dis Prevent & Toxicol, Morkhoj Bygade 19, DK-2860 Soborg, Denmark..
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Low-dose developmental exposure to bisphenol A alters the femoral bone geometry in wistar rats2016Ingår i: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 164, s. 339-346Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Bisphenol A (BPA) is a chemical produced in large volumes for use in manufacturing of consumer products and industrial applications, and an endocrine disruptor known to affect several hormonal systems. Bone produces hormones and is additionally a sensitive hormone target tissue, and is thus potentially sensitive to low doses of endocrine disruptors such as BPA, especially during development. Methods: 110 pregnant Wistar rats were gavaged with 0; 25 mu g; 250 mu g; 5000 mu g or 50,000 mu g BPA/kg bodyweight (bw)/day from gestational day 7 until weaning at postnatal day 22. The three-month-old offspring were sacrificed and right femurs collected for length measurements, geometrical measurements by peripheral quantitative computed tomography (pQCT), as well as for analyses of biomechanical properties using the three-point-bending method. Results: The femur was elongated in female offspring of dams exposed to 25 or 5000 mu g BPA/kg bw/day (1.8% and 2.1%, respectively), and increased cortical thickness (4.7%) was observed in male offspring of dams exposed to 25 mu g BPA/kg bw/day, compared to controls (p < 0.005). The biomechanical properties of the bone were not significantly altered. Conclusions: In utero and lactational exposure to the lowest BPA dose used in this study altered femoral geometry in both male and female offspring. This was observed at 25 mu g BPA/kg bw/day, a dose lower than the Human Equivalent Dose (HED) applied by EFSA to set a temporary TDI (609 mu g BPA/kg bw/day), and far lower than the No-Observed-Adverse-Effect-Level (NOAEL) (5000 mu g BPA/kg bw/day) on which the US FDA TDI is based.

  • 266.
    Lejonklou, Margareta Halin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Dunder, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Bladin, Emelie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Pettersson, Vendela
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Rönn, Monika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Waldén, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Effects of Low-Dose Developmental Bisphenol A Exposure on Metabolic Parameters and Gene Expression in Male and Female Fischer 344 Rat Offspring.2017Ingår i: Journal of Environmental Health Perspectives, ISSN 0091-6765, E-ISSN 1552-9924, Vol. 125, nr 6, artikel-id 067018Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Bisphenol A (BPA) is an endocrine-disrupting chemical that may contribute to development of obesity and metabolic disorders. Humans are constantly exposed to low concentrations of BPA, and studies support that the developmental period is particularly sensitive.

    OBJECTIVES: The aim was to investigate the effects of low-dose developmental BPA exposure on metabolic parameters in male and female Fischer 344 (F344) rat offspring.

    METHODS: Pregnant F344 rats were exposed to BPA via their drinking water, corresponding to (BPA0.5; ) or (BPA50; ), from gestational day (GD) 3.5 until postnatal day (PND) 22, and controls were given vehicle (). Body weight (BW), adipose tissue, liver (weight, histology, and gene expression), heart weight, and lipid profile were investigated in the 5-wk-old offspring.

    RESULTS: Males and females exhibited differential susceptibility to the different doses of BPA. Developmental BPA exposure increased plasma triglyceride levels ( compared with , females BPA50 ; compared with , males BPA0.5 ) in F344 rat offspring compared with controls. BPA exposure also increased adipocyte cell density by 122% in inguinal white adipose tissue (iWAT) of female offspring exposed to BPA0.5 compared with controls ( number of adipocytes/HPF compared with number of adipocytes/HPF; ) and by 123% in BPA0.5 females compared with BPA50 animals ( number of adipocytes/high power field (HPF) compared with number of adipocytes/HPF; ). In iWAT of male offspring, adipocyte cell density was increased by 129% in BPA50-exposed animals compared with BPA0.5-exposed animals ( number of adipocytes/HPF compared with number of adipocytes/HPF; ). Furthermore, the expression of genes involved in lipid and adipocyte homeostasis was significantly different between exposed animals and controls depending on the tissue, dose, and sex.

    CONCLUSIONS: Developmental exposure to of BPA, which is 8-10 times lower than the current preliminary EFSA (European Food Safety Authority) tolerable daily intake (TDI) of and is within the range of environmentally relevant levels, was associated with sex-specific differences in the expression of genes in adipose tissue plasma triglyceride levels in males and adipocyte cell density in females when F344 rat offspring of dams exposed to BPA at were compared with the offspring of unexposed controls.

  • 267.
    Lejonklou, Margareta Halin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Dunder, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Bladin, Emelie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Rönn, Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism. Uppsala Univ, Publ Hlth & Caring Sci, Uppsala, Sweden.
    Lind, monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Waldén, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Adipose tissue and metabolic homeostasis in Fischer F344 rats, exposed to developmental low doses of bisphenol A, are affected in a gender specific and non-monotonic manner2015Ingår i: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 238, nr 2, s. S253-S253Artikel i tidskrift (Övrigt vetenskapligt)
  • 268.
    Lejonklou, Margareta Halin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Botling, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Björklund, Peyman
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Experimentell kirurgi.
    Bisphenol A increases cortisol production by enhancing phosphorylation of CREB in normal human adrenocortical cells2014Ingår i: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 229, s. S243-S243Artikel i tidskrift (Övrigt vetenskapligt)
  • 269.
    Lejonklou, Margareta Halin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Botling, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Björklund, Peyman
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Experimentell kirurgi.
    Induction of LINE-1 promoter hypomethylation, a hallmark of tumorigenesis, in normal human adrenocortical cells by Bisphenol A2014Ingår i: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 229, s. S149-S149Artikel i tidskrift (Övrigt vetenskapligt)
  • 270.
    Lejonklou, Margareta Halin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Karimullina, Elina
    Larsson, Sune
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Lind, Thomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Jacobson Rasmusson, Annica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Rönn, Monika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Blumberg, Bruce
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Does developmental exposure to bisphenol A induce bone and adipose tissue disturbances?2014Ingår i: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 229, s. S243-S243Artikel i tidskrift (Övrigt vetenskapligt)
  • 271.
    Lejonklou, Margareta Halin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Lind, Thomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Rasmusson, Annica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Larsson, Sune
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Lind, Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Developmental low-dose exposure to bisphenol A results in gender-specific and non-monotonic effects on Fischer F344 rat bone2015Ingår i: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 238, nr 2, s. S255-S255Artikel i tidskrift (Övrigt vetenskapligt)
  • 272. Levänen, Bettina
    et al.
    Bhakta, Nirav R
    Torregrosa Paredes, Patricia
    Barbeau, Rebecca
    Hiltbrunner, Stefanie
    Pollack, Joshua L
    Sköld, C Magnus
    Svartengren, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Grunewald, Johan
    Gabrielsson, Susanne
    Eklund, Anders
    Larsson, Britt-Marie
    Woodruff, Prescott G
    Erle, David J
    Wheelock, Åsa M
    Altered microRNA profiles in bronchoalveolar lavage fluid exosomes in asthmatic patients.2013Ingår i: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 131, nr 3, s. 894-903Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Asthma is characterized by increased airway narrowing in response to nonspecific stimuli. The disorder is influenced by both environmental and genetic factors. Exosomes are nanosized vesicles of endosomal origin released from inflammatory and epithelial cells that have been implicated in asthma. In this study we characterized the microRNA (miRNA) content of exosomes in healthy control subjects and patients with mild intermittent asthma both at unprovoked baseline and in response to environmental challenge.

    OBJECTIVE: To investigate alterations in bronchoalveolar lavage fluid (BALF) exosomal miRNA profiles due to asthma, and following subway air exposure.

    METHODS: Exosomes were isolated from BALF from healthy control subjects (n = 10) and patients with mild intermittent asthma (n = 10) after subway and control exposures. Exosomal RNA was analyzed by using microarrays containing probes for 894 human miRNAs, and selected findings were validated with quantitative RT-PCR. Results were analyzed by using multivariate modeling.

    RESULTS: The presence of miRNAs was confirmed in exosomes from BALF of both asthmatic patients and healthy control subjects. Significant differences in BALF exosomal miRNA was detected for 24 miRNAs with a subset of 16 miRNAs, including members of the let-7 and miRNA-200 families, providing robust classification of patients with mild nonsymptomatic asthma from healthy subjects with 72% cross-validated predictive power (Q(2) = 0.72). In contrast, subway exposure did not cause any significant alterations in miRNA profiles.

    CONCLUSION: These studies demonstrate substantial differences in exosomal miRNA profiles between healthy subjects and patients with unprovoked, mild, stable asthma. These changes might be important in the inflammatory response leading to bronchial hyperresponsiveness and asthma.

  • 273. Lim, Fang Lee
    et al.
    Hashim, Zailina
    Md Said, Salmiah
    Than, Leslie Thian Lung
    Hashim, Jamal Hisham
    Norbäck, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Fractional exhaled nitric oxide (FeNO) among office workers in an academic institution, Malaysia - associations with asthma, allergies and office environment.2016Ingår i: Journal of Asthma, ISSN 0277-0903, E-ISSN 1532-4303, Vol. 53, nr 2, s. 170-178Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: There are few studies on fractional exhaled nitric oxide (FeNO) and respiratory symptoms among adults in tropical areas. The aim was to study associations between FeNO and selected personal factors, respiratory symptoms, allergies, office characteristics and indoor office exposures among office workers (n = 460) from a university in Malaysia.

    METHODS: Information on health was collected by a questionnaire, skin prick test and FeNO measurement. Temperature, relative air humidity, carbon monoxide and carbon dioxide were measured in the offices. Settled dust was vacuumed in the offices and analyzed for endotoxin, (1,3)-β-glucan and house dust mites allergens, namely Dermatophagoides pteronyssinus (Der p 1) and Dermatophagoides farinae (Der f 1). Two-level linear mixed models and multiple logistic regression were used to analyze the associations.

    RESULTS: One-fourth (25.9%) of the office workers had elevated FeNO level (≥25 ppb) and 61.5% had HDM, cat, seafood or pollen allergy. Male gender (p < 0.001), current smoking (p = 0.037), height (p < 0.001) and atopy (p < 0.001) were associated with FeNO. The amount of vacuumed dust was associated with FeNO among atopic subjects (p = 0.009). Asthma and rhinitis symptoms were associated with FeNO (p < 0.05), especially among atopic subjects. In particular, a combination of atopy and elevated FeNO were associated with doctor-diagnosed asthma (p < 0.001), rhinitis (p < 0.001) and airway symptoms last 12 months (p < 0.001).

    CONCLUSION: Gender, smoking, height and atopy are important risk factors for elevated FeNO levels. A combination of allergy testing and FeNO measurement could be useful in respiratory illness epidemiology studies and patient investigations in tropical areas.

  • 274. Lim, Fang Lee
    et al.
    Hashim, Zailina
    Than, Leslie Thian Lung
    Said, Salmiah Md
    Hashim, Jamal Hisham
    Norbäck, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Asthma, Airway Symptoms and Rhinitis in Office Workers in Malaysia: Associations with House Dust Mite (HDM) Allergy, Cat Allergy and Levels of House Dust Mite Allergens in Office Dust2015Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 4, artikel-id e0124905Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A prevalence study was conducted among office workers in Malaysia (N= 695). The aim of this study was to examine associations between asthma, airway symptoms, rhinitis and house dust mites (HDM) and cat allergy and HDM levels in office dust. Medical data was collected by a questionnaire. Skin prick tests were performed for HDM allergens (Dermatophagoides pteronyssinus, Dermatophagoides farinae) and cat allergen Felis domesticus. Indoor temperature and relative air humidity (RH) were measured in the offices and vacuumed dust samples were analyzed for HDM allergens. The prevalence of D. pteronyssinus, D. farinae and cat allergy were 50.3%, 49.0% and 25.5% respectively. Totally 9.6% had doctor-diagnosed asthma, 15.5% had current wheeze and 53.0% had current rhinitis. The Der p 1 (from D. pteronyssinus) and Der f 1 (from D. farinae) allergens levels in dust were 556 ng/g and 658 ng/g respectively. Statistical analysis was conducted by multilevel logistic regression, adjusting for age, gender, current smoking, HDM or cat allergy, home dampness and recent indoor painting at home. Office workers with HDM allergy had more wheeze (p= 0.035), any airway symptoms (p= 0.032), doctor-diagnosed asthma (p= 0.005), current asthma (p= 0.007), current rhinitis (p= 0.021) and rhinoconjuctivitis (p< 0.001). Cat allergy was associated with wheeze (p= 0.021), wheeze when not having a cold (p= 0.033), any airway symptoms (p= 0.034), doctor-diagnosed asthma (p= 0.010), current asthma (p= 0.020) and nasal allergy medication (p= 0.042). Der f 1 level in dust was associated with daytime breathlessness (p= 0.033) especially among those with HDM allergy. Der f 1 levels were correlated with indoor temperature (p< 0.001) and inversely correlated with RH (p<0.001). In conclusion, HDM and cat allergies were common and independently associated with asthma, airway symptoms and rhinitis. Der f 1 allergen can be a risk factor for daytime breathlessness.

  • 275.
    Lim, Fang-Lee
    et al.
    Univ Putra Malaysia, Fac Med & Hlth Sci, Dept Environm & Occupat Hlth, Upm Serdang 43400, Selangor, Malaysia..
    Hashim, Zailina
    Univ Putra Malaysia, Fac Med & Hlth Sci, Dept Environm & Occupat Hlth, Upm Serdang 43400, Selangor, Malaysia..
    Said, Salmiah Md
    Univ Putra Malaysia, Fac Med & Hlth Sci, Dept Community Hlth, Upm Serdang 43400, Selangor, Malaysia..
    Than, Leslie Thian-Lung
    Univ Putra Malaysia, Fac Med & Hlth Sci, Dept Med Microbiol & Parasitol, Upm Serdang 43400, Selangor, Malaysia..
    Hashim, Jamal Hisham
    UKM Med Ctr, UNU IIGH, Kuala Lumpur 56000, Malaysia.;Natl Univ Malaysia, UKM, Dept Community Hlth, Kuala Lumpur 50300, Malaysia..
    Norbäck, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Sick building syndrome (SBS) among office workers in a Malaysian university - Associations with atopy, fractional exhaled nitric oxide (FeNO) and the office environment2015Ingår i: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 536, s. 353-361Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There are few studies on sick building syndrome (SBS) including clinical measurements for atopy and fractional exhaled nitric oxide (FeNO). Our aim was to study associations between SBS symptoms, selected personal factors, office characteristics and indoor office exposures among office workers from a university in Malaysia. Health data were collected by a questionnaire (n = 695), skin prick test (SPT) (n = 463) and FeNO test (n = 460). Office settled dust was vacuumed and analyzed for endotoxin, (1,3)-beta-glucan and house dust mites (HDM) allergens group 1 namely Dermatophagoides pteronyssinus (Der p 1) and Dermatophagoides farinae (Der f 1). Office indoor temperature, relative air humidity (RH), carbon monoxide (CO) and carbon dioxide (CO2) were measured by a direct reading instrument. Associations were studied by two-levelsmultiple logistic regression with mutual adjustment and stratified analysis. The prevalence of weekly dermal, mucosal and general symptoms was 11.9%, 16.0% and 23.0% respectively. A combination of SPT positivity (allergy to HDM or cat) and high FeNO level (>= 25 ppb) was associated with dermal (p = 0.002), mucosal (p <0.001) and general symptoms (p = 0.05). Der f1 level in dust was associated with dermal (p < 0.001), mucosal (p < 0.001) and general (p = 0.02) symptoms. Among those with allergy to D. farinae, associations were found between Der f 1 levels in dust and dermal (p = 0.003), mucosal (p = 0.001) and general symptoms (p = 0.007). Office-related symptoms were associated with Der f 1 levels in dust (p = 0.02), low relative air humidity (p = 0.04) and high office temperature (p = 0.05). In conclusion, a combination of allergy to cat or HDM and high FeNO is a risk factor for SBS symptoms. Der f 1 allergen in dust can be a risk factor for SBS in the office environment, particularly among those sensitized to Der f 1 allergen.

  • 276.
    Lin, Zhijin
    et al.
    Fudan Univ, Sch Publ Hlth, Dept Environm Hlth, Key Lab Publ Hlth Safety,Minist Educ, Shanghai 200032, Peoples R China..
    Norbäck, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Wang, Tingting
    Xinjiang Med Univ, Sch Publ Hlth, Dept Maternal Child & Adolescent Hlth, Urumqi 830011, Peoples R China..
    Zhang, Xin
    Shanxi Univ, Inst Environm Sci, Taiyuan 030006, Peoples R China..
    Shi, Jingjin
    Fudan Univ, Sch Publ Hlth, Dept Environm Hlth, Key Lab Publ Hlth Safety,Minist Educ, Shanghai 200032, Peoples R China..
    Kan, Haidong
    Fudan Univ, Sch Publ Hlth, Dept Environm Hlth, Key Lab Publ Hlth Safety,Minist Educ, Shanghai 200032, Peoples R China..
    Zhao, Zhuohui
    Fudan Univ, Sch Publ Hlth, Dept Environm Hlth, Key Lab Publ Hlth Safety,Minist Educ, Shanghai 200032, Peoples R China..
    The first 2-year home environment in relation to the new onset and remission of asthmatic and allergic symptoms in 4246 preschool children2016Ingår i: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 553, s. 204-210Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The home environment can influence childhood allergies and respiratory health but there is little information on associations between early life exposure at home and new onset. and remission of the asthmatic or allergic symptoms in preschool children. A questionnaire survey was performed in a random cluster sample of 4246 preschool children in Urumqi, China. Information on the home environment (perceptions of odors and indicators of pollution sources) and children's health (wheeze, rhinitis and eczema) was collected for the first 2 years of life and the last year (before answering the questionnaire) from one of the parents or another guardian of the child. Associations between the home environment the first 2 years of life and new onset and remission of childhood symptoms were analyzed by multiple logistic regression. Home environment factors reported for the first 2 years of life were consistently positively associated with new onset of symptoms and negatively associated with remission of symptoms. Visible mold (OR 1.46,95% Cl 1.12-1.90), moldy odor (OR 2.15, 95% Cl 1.45-3.18), air dryness (OR 1.31, 95% Cl 1.08-1.59), stuffy odor (OR 1.25, 95% Cl 1.01-1.54) and parental smoking (OR 1.36, 95% Cl 1.13-1.65) were associated with new onset of symptoms. These factors were negatively associated with the remission of symptoms. In conclusion, mold contamination at home (moldy odor/visible mold), poor indoor air quality (stuffy odor, air dryness) and exposure to environmental tobacco smoke (ETS) in the first 2 years of life can increase the incidence of asthmatic and allergic symptoms and decrease the remission from these symptoms in preschool children. 

  • 277. Lin, Zhijing
    et al.
    Wang, Tingting
    Norbäck, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Kan, Haidong
    Sundell, Jan
    Zhao, Zhuohui
    Sick building syndrome, perceived odors, sensation of air dryness and indoor environment in Urumqi, China2014Ingår i: Chinese Science Bulletin, ISSN 1001-6538, E-ISSN 1861-9541, Vol. 59, nr 35, s. 5153-5160Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In order to evaluate the perceived home indoor air quality, as well as sick building syndrome (SBS) in areas with typical arid continental climate such as Urumqi, northwest of China, a cross-sectional study including 4,260 parents of children (1-8 years) was performed by a questionnaire survey in winter season in 2011. The sensation of air dryness (weekly/sometimes) in the last 3 months had the highest proportion of reports by more than half of the parents (57.4 %), followed by perceived stuffy odor (40.6 %), unpleasant odor (27.0 %), tobacco smoke odor (25.5 %), sensation of humid air (17.9 %), pungent odor (11.7 %) and moldy odor (9.5 %), respectively. The prevalence of SBS symptoms in the same time period was 40.4 % for general symptom, 47.7 % for mucosal symptom and 9.5 % for skin symptom, respectively. There were significant associations between perceived odors/sensation of air dryness and SBS symptoms (ORs range 1.39-1.42). Additionally, the OR values increased with an increase of the OH score (P < 0.05). Dampness, the presence of cockroaches and mosquitoes/flies, prenatal exposure to decoration and close to traffic were all risk factors of SBS symptoms. However, frequently putting bedding to sunshine was potentially a protective factor. In conclusion, adults' perceptions of odors and sensation of air dryness are related to SBS symptoms and home environmental factors in Urumqi, China.

  • 278. Lin, Zhijing
    et al.
    Zhao, Zhuohui
    Xu, Huihui
    Zhang, Xin
    Wang, Tingting
    Kan, Haidong
    Norbäck, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Home Dampness Signs in Association with Asthma and Allergic Diseases in 4618 Preschool Children in Urumqi, China-The Influence of Ventilation/Cleaning Habits2015Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 7, artikel-id e0134359Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There is an increasing prevalence of childhood asthma and allergic diseases in mainland of China. Few studies investigated the indoor dampness, ventilation and cleaning habits and their interrelationship with childhood asthma and allergic diseases. A large-scale cross-sectional study was performed in preschool children in Urumqi, China. Questionnaire was used to collect information on children's health, home dampness and ventilation/cleaning (V/C) habits. Multiple logistic regressions were applied to analyze the associations between childhood asthma/allergic diseases and each sign of home dampness, dampness levels, each V/C habit and total V/C scores. The associations between dampness and health were further performed by strata analyses in two groups with low and high V/C scores. Totally 4618 (81.7%) of 5650 children returned the questionnaire. Reports on home dampness were most common for water condensation on windows (20.8%) followed by damp beddings (18.0%). The most common ventilation measure was the use of exhaust fan in bathroom (59.3%), followed by daily home cleaning (48.3%), frequently putting beddings to sunshine (29.9%) and frequently opening windows in winter (8.4%). There were positive associations between the 6 signs of home dampness and children's health particularly the symptoms last 12 months. By comparing with the reference dampness level (dampness scored 0), both the low dampness (scored 1 similar to 2) level and the high dampness level (scored 3 similar to 6) showed significantly increasing associations with childhood symptoms. There were crude negative associations between V/C habits and childhood health but not significant adjusting for home dampness levels. The risks of home dampness on children's health were lower in the group with higher V/C score but the differences were not statistically significant. Home dampness is a potential risk factor for childhood asthma and allergic symptoms in preschool children in Urumqi, China. No significant effects were observed for ordinary home ventilation and cleaning habits in reducing the risks of home dampness on childhood asthma and allergic diseases in Urumqi, China.

  • 279.
    Lind, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Can Persistent Organic Pollutants And Plastic-Associated Chemicals Cause Cardiovascular Disease?2012Ingår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 271, nr 6, s. 537-553Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    During the last decade, associations between persistent organic pollutants (POPs), such as polychlorinated biphenyls, dioxins and pesticides, and cardiovascular (CV) risk factors and overt CV disease (CVD) have been reported in humans. Recently, associations between plastic-associated chemicals (PACs), such as bisphenol A and phthalates, and CVD have also begun to emerge. Several approaches to evaluating such associations have been used: accidents with a high level of exposure, occupational exposure studies, geographical studies of subjects living near a contaminated area and traditional case-control or cohort studies with measurements of circulating levels of different environmental contaminants in the general population. Exposure to POPs has consistently been associated with diabetes using all the approaches described above, including prospective studies. The evidence regarding associations between exposure to POPs and other CV risk factors, such as hypertension, obesity and lipids, is less strong, and is mainly based on cross-sectional data. Associations between overt CVD and POPs have been reported using all the above approaches, but prospective data from population-based studies are still lacking to provide firm evidence of an important and independent role of POP exposure in the pathogenesis of CVD. Nevertheless, taken together, current evidence suggests that further longitudinal and experimental studies should be conducted to investigate the effect of exposure to both POPs and PACs, such as bisphenol A and phthalates.

  • 280.
    Lind, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Lejonklou, Margareta H
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Dunder, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Bergman, Åke
    Guerrero-Bosagna, Carlos
    Lampa, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Lee, Hong Kyu
    Legler, Juliette
    Nadal, Angel
    Pak, Youngmi Kim
    Phipps, Richard P
    Vandenberg, Laura N
    Zalko, Daniel
    Ågerstrand, Marlene
    Öberg, Mattias
    Blumberg, Bruce
    Heindel, Jerrold J
    Birnbaum, Linda S
    Uppsala Consensus Statement on Environmental Contaminants and the Global Obesity Epidemic2016Ingår i: Journal of Environmental Health Perspectives, ISSN 0091-6765, E-ISSN 1552-9924, Vol. 124, nr 5, s. A81-A83Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    From the lectures presented at the 2nd International Workshop on Obesity and Environmental Contaminants, which was held in Uppsala, Sweden, on 8–9 October 2015, it became evident that the findings from numerous animal and epidemiological studies are consistent with the hypothesis that environmental contaminants could contribute to the global obesity epidemic. To increase awareness of this important issue among scientists, regulatory agencies, politicians, chemical industry management, and the general public, the authors summarize compelling scientific evidence that supports the hypothesis and discuss actions that could restrict the possible harmful effects of environmental contaminants on obesity.

  • 281.
    Lind, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ng, Esther
    Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.
    Lindgren, Cecilia
    Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, USA.
    Salihovic, Samira
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    van Bavel, Bert
    MTM Research Centre, School of Science and Technology, Örebro University, Sweden.
    Mahajan, Anubha
    Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
    Lampa, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Morris, Andrew P
    Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Department of Biostatistics, University of Liverpool, Liverpool, UK.
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Genetic and methylation variation in the CYP2B6 gene is related to circulating p,p'-dde levels in a population-based sample2017Ingår i: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 98, s. 212-218Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: Since the metabolism of the organochlorine pesticide dichlorodiphenyltrichloroethane (DDT) is not fully known in humans, we evaluated if circulating levels of a major breakdown product of DDT, p,p'-DDE, were related to genome-wide genetic and methylation variation in a population-based sample.

    METHODS: In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (1016 subjects all aged 70), circulating levels of p,p'-DDE were analyzed by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/HRMS). Genetic variants were genotyped and imputed (1000 Genomes reference, March 2012 release). Methylation sites were assayed using the Illumina HumanMethylation450 array in whole blood. A genome-wide association study (GWAS) approach was applied.

    RESULTS: Evidence for genome-wide significant association with p,p'-DDE levels was observed only for a locus at chromosome 19 corresponding to the CYP2B6 gene (lead SNP rs7260538). Subjects being homozygote for the G allele showed a median level of 472ng/g lipid, while the corresponding level for those being homozygote for the T allele was 192ng/g lipid (p=1.5×10(-31)). An analysis conditioned on the lead SNP disclosed a distinct signal in the same gene (rs7255374, position chr19:41520351; p=2.2×10(-8)). A whole-genome methylation analysis showed one significant relationship vs. p,p'-DDE levels (p=6.2×10(-9)) located 7kb downstream the CYP2B6 gene (cg27089200, position chr19:41531976). This CpG-site was also related to the lead SNP (p=3.8×10(-35)), but mediated only 4% of the effect of the lead SNP on p,p'-DDE levels.

    CONCLUSION: Circulating levels of p,p'-DDE were related to genetic variation in the CYP2B6 gene in the general elderly population. DNA methylation in this gene is not closely linked to the p,p'-DDE levels.

  • 282.
    Lind, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Penell, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Luttropp, Karin
    Nordfors, Louise
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Axelsson, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Salihovic, Samira
    van Bavel, Bert
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lind, P Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Global DNA hypermethylation is associated with high serum levels of persistent organic pollutants in an elderly population2013Ingår i: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 59, s. 456-461Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Dioxin exposure has experimentally been associated with changes in DNA methylation, an epigenetic change that is associated with disease. The present study aims to investigate if serum levels of dioxin and other persistent environmental pollutants are related to global DNA methylation in a human sample. In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (all aged 70), global DNA methylation was measured by the Luminometric Methylation Assay in 524 subjects. Twenty-three different POPs, including 16 PCBs, five pesticides, one dioxin (OCDD) and one brominated flame retardant (BDE47) were analysed by HRGC/HRMS. Ten single nucleotide polymorphisms (SNPs) in the Aryl hydrocarbon (Ah)-receptor were analysed by mini-sequencing. High levels of toxic equivalency (TEQ) for PCBs and dioxin were associated with DNA hypermethylation (p=0.030). This was mainly attributed to coplanar non-ortho PCBs. While no significant associations were found between DNA methylation and SNPs in the Ah-receptor, an interaction was found between the SNP rs2237297 and TEQ so that TEQ was associated with hypermethylation (p=0.009) only in subjects with one G-allele (n=103). Also high levels of the PCB126 congener, the OCDD, and the pesticide metabolite p,p'-DDE were related to DNA hypermethylation (p=0.01, 0.03 and 0.003, respectively). In conclusion, in a sample of elderly subjects, high TEQ including PCBs and the dioxin OCDD and high serum levels of PCB126, OCDD, and p,p'-DDE were related to global DNA hypermethylation in a cross-sectional analysis.

  • 283.
    Lind, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Penell, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Axelsson, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Morris, Andrew P
    Lindgren, Cecilia
    Salihovic, Samira
    van Bavel, Bert
    Lind, P Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Genetic variation in the CYP1A1 gene is related to circulating PCB118 levels in a population-based sample2014Ingår i: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 133, s. 135-140Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Several of the polychlorinated biphenyls (PCBs), i.e. the dioxin-like PCBs, are known to induce the P450 enzymes CYP1A1, CYP1A2 and CYP1B1 by activating the aryl hydrocarbon receptor (Ah)-receptor. We evaluated if circulating levels of PCBs in a population sample were related to genetic variation in the genes encoding these CYPs. In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (1016 subjects all aged 70), 21 SNPs in the CYP1A1, CYP1A2 and CYP1B1 genes were genotyped. Sixteen PCB congeners were analysed by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/ HRMS). Of the investigated relationships between SNPs in the CYP1A1, CYP1A2 and CYP1B1 and six PCBs (congeners 118, 126, 156, 169, 170 and 206) that captures >80% of the variation of all PCBs measured, only the relationship between CYP1A1 rs2470893 was significantly related to PCB118 levels following strict adjustment for multiple testing (p=0.00011). However, there were several additional SNPs in the CYP1A2 and CYP1B1 that showed nominally significant associations with PCB118 levels (p-values in the 0.003-0.05 range). Further, several SNPs in the CYP1B1 gene were related to both PCB156 and PCB206 with p-values in the 0.005-0.05 range. Very few associations with p<0.05 were seen for PCB126, PCB169 or PCB170. Genetic variation in the CYP1A1 was related to circulating PCB118 levels in the general elderly population. Genetic variation in CYP1A2 and CYP1B1 might also be associated with other PCBs.

  • 284.
    Lind, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Salihovic, Samira
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lampa, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Mixture effects of 30 environmental contaminants on incident metabolic syndrome: A prospective study2017Ingår i: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 107, s. 8-15Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Several cross-sectional studies have linked different environmental contaminants to the metabolic syndrome (MetS). However, mixture effects have not been investigated and no prospective studies exist regarding environmental contaminants and the MetS.

    Objectives: To study mixture effects of contaminants on the risk of incident MetS in a prospective fashion.

    Methods: Our sample consisted of 452 subjects from the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study (50% women, all aged 70 years) free from the MetS at baseline, being followed for 10 years. At baseline, 30 different environmental contaminants were measured; 6 polychlorinated biphenyls (PCBs), 3 organochlorine (OC) pesticides, one dioxin, one polybrominated diphenyl ether (all in plasma), 8 perfluoroalkyl substances (in plasma) and 11 metals (in whole blood). The MetS was defined by the ATPIII/NCEP criteria. Gradient boosted Classification and Regression Trees (CARTs) was used to evaluate potential synergistic and additive mixture effects on incident MetS.

    Results: During 10-year follow-up, 92 incident cases of the MetS occurred. PCB126, PCB170, hexachlorobenzene (HCB) and PCB118 levels were all associated with incident MetS in an additive fashion (OR 1.73 for a change from 10th to 90th percentile (95% CI 1.24-3.04) for PCB126, OR 0.63 (0.42-0.78) for PCB170, OR 1.44 (1.09-2.20) for HCB and OR 1.46 (1.13-2.43) for PCB118). No synergistic effects were found.

    Conclusion: A mixture of environmental contaminants, with PCB126, PCB170, HCB and PCB118 being the most important, showed associations with future development of the MetS in an additive fashion in this prospective study. Thus, mixture effects of environmental contaminants could contribute to the development of cardiometabolic derangements.

  • 285.
    Lind, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Salihovic, Samira
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Univ Orebro, Orebro.
    Van Bavel, B.
    Univ Orebro, Orebro, Switzerland..
    Lind, Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Circulating levels of perfluorinated compounds and left ventricular geometry2015Ingår i: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 238, nr 2, s. S93-S93Artikel i tidskrift (Övrigt vetenskapligt)
  • 286.
    Lind, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Salihovic, Samira
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    van Bavel, Bert
    Lind, Monica P.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Circulating levels of perfluoroalkyl substances and prevalent diabetes in the elderly2014Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 57, nr 3, s. 473-479Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Several environmental contaminants, such as polychlorinated biphenyls, dioxins, bisphenol A and phthalates, have been linked to diabetes. We therefore investigated whether other kinds of contaminants, perfluoroalkyl substances (PFAS), also called perfluorinated compounds (PFCs), are also associated with diabetes. The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study investigated 1,016 men and women aged 70 years. Seven PFAS were detected in almost all participant sera by ultra-high performance liquid chromatograph/tandem mass spectrometry. Diabetes was defined as use of hypoglycaemic agents or fasting glucose > 7.0 mmol/l. 114 people had diabetes. In the linear analysis, no significant relationships were seen between the seven PFAS and prevalent diabetes. However, inclusion of the quadratic terms of the PFAS revealed a significant non-linear relationship between perfluorononanoic acid (PFNA) and diabetes, even after adjusting for multiple confounders (OR 1.96, 95% CI 1.19, 3.22, p = 0.008 for the linear term and OR 1.25, 95% CI 1.08, 1.44, p = 0.002 for the quadratic term). Perfluorooctanoic acid (PFOA) also showed such a relationship (p = 0.01). PFOA was related to the proinsulin/insulin ratio (a marker of insulin secretion), but none of the PFAS was related to the HOMA-IR (a marker of insulin resistance) following adjustment for multiple confounders. PFNA was related to prevalent diabetes in a non-monotonic fashion in this cross-sectional study, supporting the view that this perfluoroalkyl substance might influence glucose metabolism in humans at the level of exposure seen in the general elderly population.

  • 287.
    Lind, Monica
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Gustafsson, Magnus
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Ekotoxikologi.
    Hermsen, Sanne A B
    Larsson, Sune
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Kyle, Carol E
    Örberg, Jan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Ekotoxikologi.
    Rhind, Stewart M
    Exposure to pastures fertilised with sewage sludge disrupts bone tissue homeostasis in sheep2009Ingår i: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 407, nr 7, s. 2200-2208Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The femurs of male and female sheep (Ovis aries), aged 18 months, bred on pastures fertilized twice annually with sewage sludge (2.25 tonnes dry matter/ha; Treated; T)) or on pastures treated with inorganic fertilizer (Control; C) were studied, using peripheral Quantitative Computed Tomography (pQCT) and the three-point bending test. Males were maintained on the respective treatments from conception to weaning and then maintained on control pastures while the females were maintained on the respective treatments until slaughter. T rams exhibited increased total bone mineral density (BMD) at the metaphyseal part of femur (+10.5%, p<0.01) compared with C rams but had a reduced total cross sectional area (CSA, -11.5%, p<0.001), trabecular CSA (-17.1%, p<0.01) and periosteal circumference (-5.7%, p<0.001). In the mid-diaphyseal part, T rams had an increased total BMD (+13.8%, p<0.0001) and stiffness (+6.4%, p<0.01) but reduced total CSA (-12.1%, p<0.0001) and marrow cavity (-25.8%, p<0.0001), relative to C rams. In ewes although pQCT analysis of neither the metaphyseal nor the mid-diaphyseal part of the female femur bones showed any significant differences with treatment, the biomechanical method revealed a reduction in load at failure (-17.3%, p<0.01) and stiffness (-10.7%, p<0.05) amongst T ewes. It is concluded that exposure to pollutants present in sewage sludge can perturb bone tissue homeostasis in sheep, but particularly in males.

  • 288.
    Lind, Monica
    et al.
    Institute of Environmental Medicine, Karolinska Institutet.
    Johansson, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Rönn, Monika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Subclinical Hypervitaminosis A in Rat: Measurements of bone mineral density (BMD) do not reveal adverse skeletal changes2006Ingår i: Chemico-Biological Interactions, ISSN 0009-2797, E-ISSN 1872-7786, Vol. 159, nr 1, s. 73-80Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We have previously shown that subclinical hypervitaminosis A in rats causes fragile bones. To begin to investigate possible mechanisms for Vitamin A action we extended our previous study. Forty-five mature female Sprague-Dawley rats were divided into three groups, each with 15 animals. They were fed a standard diet containing 12IU Vitamin A per g pellet (control, C), or a standard diet supplemented with 120 IU ("10xC") or 600 IU ("50xC") Vitamin A/g pellet for 12 weeks. At the end of the study, serum retinyl esters were elevated 4- and 20-fold. Although neither average food intake nor final body weights were significantly different between groups, a dose-dependent reduction in serum levels of Vitamin D and E, but not Vitamin K, was found. In the 50xC-group the length of the humerus was the same as in controls, but the diameter was reduced (-4.1%, p<0.05). Peripheral quantitative computed tomography (pQCT) at the diaphysis showed that bone mineral density (BMD) was unchanged and that periosteal circumference had decreased significantly (-3.7%, p<0.05). Ash weight of the humerus was not affected, but since bone volume decreased, volumetric BMD, as measured by the bone ash method, even increased (+2.5%, p<0.05). In conclusion, interference with other fat-soluble Vitamins is a possible indirect mechanism of Vitamin A action. Moreover, BMD measurements do not reveal early adverse skeletal changes induced by moderate excesses of Vitamin A in rats. Since the WHO criterium for osteoporosis is based on BMD, further studies are warranted to examine whether this is also true in humans.

  • 289.
    Lind, Monica
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Circulating levels of bisphenol A and phthalates are related to carotid atherosclerosis in the elderly2011Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 218, nr 1, s. 207-213Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and objective: Bisphenol A (BPA) levels have previously been associated with coronary heart disease (CHD). Since CHD is an atherosclerotic disease, we investigated if circulating levels of BPA and phthalate metabolites are related to atherosclerosis in a cross-sectional study. Methods: In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (1016 subjects all aged 70), the prevalence of overt plaques and echogenectity (grey scale median, GSM) of carotid artery plaques were recorded by ultrasound in both of the carotid arteries. The thickness (IMT) and echogenicity (IM-GSM) of the intima-media complex were also measured. Bisphenol A (BPA) and 10 phthalate metabolites were analyzed in serum by a API 4000 liquid chromatograph/tandem mass spectrometer. Results: Mono-methyl phthalate (MMP) was related to carotid plaques in an inverted U-shaped manner. This pattern was significant after adjustment for gender, body mass index, blood glucose, blood pressure, HDL and LDL-cholesterol, serum triglycerides, smoking, antihypertensive treatment and statin use (p = 0.004). High levels of BPA, mono-isobutyl phthalate (MiBP) and MMP were associated with an echogenic IM-GSM and plaque GSM, while high levels of mono-2-ethylhexyl phthalate (MEHP) were associated with an echolucent IM-GSM and plaque GSM (p < 0.0001 after adjustment). Conclusion: The phthalate metabolite MMP was related to atherosclerotic plaques in an inverted U-shaped manner independently of CV risk factors. Some phthalates and BPA were also related to the echogenicity of the plaques, suggesting a role for plaque-associated chemicals in atherosclerosis.

  • 290.
    Lind, Monica
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Olsén, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Circulating levels of metals are related to carotid atherosclerosis in elderly2012Ingår i: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 1, nr 416, s. 80-88Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of this study was to investigate if blood levels of trace and/or heavy metals are related to atherosclerosis in a cross-sectional study in elderly. In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (1016 subjects, all aged 70), the prevalence of carotid artery plaques was recorded by ultrasound. The numbers of carotid arteries with plaques (0, 1 or 2) were recorded. Also the thickness (IMT) and gray scale (IM-GSM) of the intima-media complex were measured together with plaque echogenicity. Eleven heavy metals and trace elements were analyzed in whole blood, using inductively coupled plasma-sector field mass spectrometry. Nickel levels were related to the number of carotid arteries with plaques in an inverted U-shaped manner after multiple adjustment for gender, waist circumference, body mass index, fasting blood glucose, systolic and diastolic blood pressure, HDL and LDL cholesterol, serum triglycerides, smoking, antihypertensive treatment and statin use (p=0.026). IM-GSM and plaque echogenicity were both inversely related to chromium in a linear fashion, and to aluminum in an inverted U-shaped manner (both p<0.0001 for IM-GSM). The relationships between metals and IMT were modest. Circulating levels of some metals, like nickel, aluminum and chromium, were related to atherosclerotic plaques or the echogenicity of the IM-GSM and overt plaques independently of cardiovascular risk factors, including lipids.

  • 291.
    Lind, Monica P.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Lee, D. -H
    Jacobs, D. R.
    Salihovic, S.
    Bavel, B. V.
    Wolff, M. S.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Circulating levels of persistent organic pollutants are related to retrospective assessment of life-time weight change2013Ingår i: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 90, nr 3, s. 998-1004Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Persistent organic pollutants (POPs) have been suggested to be linked to obesity. We have previously shown that less-chlorinated PCBs were positively related to fat mass, while highly-chlorinated PCBs were inversely related to obesity.Objective: The aim of the present evaluation is to investigate the relationship between retrospective assessed life-time change in body weight (20-70. years) with circulating POP levels measured at age 70. years.Methods: 1016 subjects aged 70. years were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUSs) study. 16 PCBs and 3 OC pesticides were analyzed using HRGC/HRMS. Current body weight was measured and participants self-reported their weight at age 20.Results: The average estimated weight change over 50. years was 14.4. kg. Both the sum of OC pesticide concentrations (4.3. kg more weight gain in quintile 5 vs. quintile 1, p< 0.0001) and the sum of the less-chlorinated PCBs were positively related to the estimated weight change (3.7. kg more weight gain in quintile 2 vs. quintile 1, non-linear relationship p=0.0015). In contrast, the sum of concentrations of highly-chlorinated PCBs were inversely related to estimated weight change (8.4. kg less weight gain in quintile 5 vs. quintile 1, p< 0.0001).Conclusion: High levels of OC pesticides and the less-chlorinated PCBs at age 70 were associated with a pronounced estimated weight change over the previous 50. years. However, the opposite was seen for highly-chlorinated PCBs. Differences in mode of action, toxicokinetics, non-linear relationships and reverse causation might explain these discrepancies.

  • 292.
    Lind, Monica P.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Olsén, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Elevated circulating levels of copper and nickel are found in elderly subjects with left ventricular hypertrophy2012Ingår i: Ecotoxicology and Environmental Safety, ISSN 0147-6513, E-ISSN 1090-2414, Vol. 86, s. 66-72Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Identified risk factors for left ventricular hypertrophy (LVH) are hypertension, diabetes and obesity. However, since these risk factors only explain a part of the variation in left ventricular mass, we investigated if trace and heavy metals might also play a role in LVH. In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, left ventricular mass index (LVMI) and relative wall thickness (RWT) were determined by echocardiography together with eleven different trace and heavy metals in 993 subjects aged 70 years. Only copper levels were significantly related to LVMI following adjustment for sex, blood pressure, antihypertensive treatment, diabetes and body mass index (BMI) (p<0.0001). However, both copper (Cu) and nickel (Ni) were related to RWT following adjustment (p<0.0001). When divided into four geometric groups, both Cu and Ni were elevated in subjects with concentric remodelling and concentric LVH, but not in those with eccentric hypertrophy, when compared to subjects with a normal left ventricle. No relationships were found for zinc, aluminium, manganese, molybdenum, mercury, lead, cadmium, cobalt or chromium. Elevated levels of copper and nickel are found in elderly subjects with LVH, especially of the concentric type, following adjustment for known risk factors for LVH.

  • 293.
    Lind, Monica P.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Penell, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Salihovic, Samira
    van Bavel, Bert
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Circulating levels of p,p '-DDE are related to prevalent hypertension in the elderly2014Ingår i: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 129, s. 27-31Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Polychlorinated biphenyls (PCBs) and dioxin given to experimental animals increase the blood pressure. We therefore investigated if circulating levels of persistent organic pollutants (POPs) were related to hypertension in a population-based sample of men and women. Methods: One thousand and sixteen subjects aged 70 years were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Twenty-three POPs were analyzed using high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS). Hypertension was defined as a systolic blood pressure >= 140 mmHg or a diastolic blood pressure >= 90 mmHg, and/or use of antihypertensive medication. Results: Seven hundred and thirty-two subjects (72%) showed hypertension. When the POPs were treated as continuous variables and adjusted for gender only, two PCBs with a low number of chlorine atoms (PCB 105 and 118) were related to prevalent hypertension. Also the OC pesticide p,p'-DDE was related to hypertension. The strongest of these associations was seen for p,p'-DDE (OR 135 for a 1 SD change, 95% CI 1.17-1.56, p < 0.0001). Following further adjustment also for BMI, smoking status, education level and exercise habits, only p,p'-DDE was still significantly related to hypertension (OR 1.23 for a 1 SD change, 95% CI 1.06-1.43, p=0.006). Conclusion: In this cross-sectional analysis of an elderly population, high levels of circulating levels of p,p'-DDE were associated with prevalent hypertension, further strengthening the experimental findings that POPs might influence blood pressure.

  • 294.
    Lind, Monica
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Salihovic, Samira
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Univ Orebro, MTM Res Ctr, Sch Sci & Technol, SE-70182 Orebro, Sweden..
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    van Bavel, B.
    Univ Orebro, MTM Res Ctr, Sch Sci & Technol, SE-70182 Orebro, Sweden..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Circulating levels of perfluoroalkyl substances and biomarkers of liver function in a large population based sample of elderly men and women from Sweden2015Ingår i: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 238, nr 2, s. S91-S91Artikel i tidskrift (Övrigt vetenskapligt)
  • 295.
    Lind, Monica
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Salihovic, Samira
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Stubleski, Jordan
    Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Kärrman, Anna
    Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Van Bavel, Bert
    Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    The changes in plasma levels of perfluoroalkyl substances (PFASs) are related to the increase in carotid intima-media thickness over 10 years2017Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 263, s. E18-E18Artikel i tidskrift (Övrigt vetenskapligt)
  • 296.
    Lind, Monica
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    van Bavel, Bert
    Salihovic, Samira
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Circulating Levels of Persistent Organic Pollutants (POPs) and Carotid Atherosclerosis in the Elderly2012Ingår i: Journal of Environmental Health Perspectives, ISSN 0091-6765, E-ISSN 1552-9924, Vol. 120, nr 1, s. 38-43Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and objective:

    Increased circulating levels of persistent organic pollutants (POPs) have been associated with myocardial infarction. Because myocardial infarction is an atherosclerotic disease, we investigated, in a cross-sectional study, whether POP levels are related to atherosclerosis.

    Methods:

    In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (n = 1,016 participants 70 years of age), the prevalence of carotid artery plaques was determined by ultrasound. The number of carotid arteries with plaques (0, 1, or 2) was recorded. Also, the intima-media thickness (IMT) and gray scale median of the intima-media complex (IM-GSM) were measured. Twenty-three POPs, comprising 16 polychlorinated biphenyls (PCBs), 5 pesticides, 1 dioxin, and 1 brominated compound (brominated diphenyl ether congener BDE-47), were analyzed by high-resolution chromatography coupled to high-resolution mass spectrometry.

    Results:

    Seven of the POPs (PCB congeners 153, 156, 157, 170, 180, 206, and 209) were significantly associated with the number of carotid arteries with plaques even after adjusting for multiple risk factors (sex, waist circumference, body mass index, fasting blood glucose, systolic and diastolic blood pressure, high-density lipoprotein and low-density lipoprotein cholesterol, serum triglycerides, smoking, antihypertensive treatment, and statin use; p = 0.002-0.0001). Highly chlorinated PCBs (congeners 194, 206, and 209) were associated with an echolucent IM-GSM (p < 0.0001 after adjustment), whereas associations between POPs and IMT were modest.

    Conclusions:

    Circulating levels of PCBs were associated with atherosclerotic plaques and echogenicity of the intima-media complex independent of cardiovascular risk factors, including lipids. This suggests that POPs may be a risk factor for myocardial infarction, but associations need to be confirmed in prospective studies.

  • 297.
    Lind, Monica
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Öberg, Denise
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Ekotoxikologi.
    Larsson, Sune
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Kyle, Carol E.
    Örberg, Jan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för fysiologi och utvecklingsbiologi, Ekotoxikologi.
    Rhind, Stewart M.
    Pregnant ewes exposed to multiple endocrine disrupting pollutants through sewage sludge-fertilized pasture show an anti-estrogenic effect in their trabecular bone2010Ingår i: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 408, nr 11, s. 2340-2346Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Pregnant ewes were maintained on pastures fertilized, twice yearly, with either sewage sludge (2.25tonnes dry matter/ha; Treated; T) or inorganic fertilizer containing equivalent amounts of nitrogen (Control; C), to determine effects on maternal and fetal bone structures, density and mechanical properties of exposure to environmental concentrations of multiple endocrine disrupting compounds (EDCs) and heavy metal pollutants. The ewes were maintained on the respective pastures from the age of about 8months until they were 4-6years of age and they were slaughtered at 110d gestation. Metaphyseal parts of adult ewe femurs exhibited a significantly reduced mean, total cross sectional area (CSA, -4%; p<0.05), lower trabecular bone mineral content (BMC, mg/mm; -18%; p<0.05), trabecular bone mineral density (BMD, mg/cm(3), -8.0%; p<0.05) and trabecular CSA, mm(2), -11.1%; p<0.05) in T compared with C animals. Femurs of T ewes were stronger than those of C ewes but this may reflect greater body weights. At the mid-diaphyseal part of the fetal bones, there was a reduction in endosteal circumference (-6.7%, p<0.05) and marrow cavity area (-13.8%, p<0.05) in the female T fetuses compared with female C fetuses. In the male fetuses the mid-diaphyseal part total bone mineral content was higher (+3.0%, p<0.05) in T than in C animals. No treatment difference in biomechanical bending was detected in the fetuses. It is concluded that ewes grazing pasture fertilized with sewage sludge exhibited an anti-estrogenic effect on their trabecular bone in the form of reduced mineral content and density, despite increased body weight. It is suggested that human exposure to low levels of multiple EDCs may have implications for bone structure and human health.

  • 298.
    Lind, P. Monica
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Endocrine-disrupting chemicals and risk of diabetes: an evidence-based review2018Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, nr 7, s. 1495-1502Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    The purpose of this study was to review the epidemiological and experimental evidence linking background exposure to a selection of environmental endocrine-disrupting chemicals (EDCs) with diabetes and impaired glucose metabolism. The review summarises the literature on both cross-sectional and prospective studies in humans, as well as experimental in vivo and in vitro studies. The findings were subjected to evidence grading according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification. We found > 40 cross-sectional and seven prospective studies regarding EDCs and risk of diabetes. Taken together, there is moderate evidence for a relationship between exposure to dichlorodiphenyldichloroethylene (p,p'-DDE), a metabolite of the pesticide dichlorodiphenyltrichloroethane, and diabetes development. Regarding polychlorinated biphenyls (PCBs), it is likely that the rodent models used are not appropriate, and therefore the evidence is poorer than for p,p'-DDE. For other EDCs, such as bisphenol A, phthalates and perfluorinated chemicals, the evidence is scarce, since very few prospective studies exist. Brominated flame retardants do not seem to be associated with a disturbed glucose tolerance. Thus, evidence is accumulating that EDCs might be involved in diabetes development. Best evidence exists for p,p'-DDE. For other chemicals, both prospective studies and supporting animal data are still lacking.

  • 299.
    Lind, P. Monica
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Riserus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Salihovic, Samira
    van Bavel, Bert
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    An environmental wide association study (EWAS) approach to the metabolic syndrome2013Ingår i: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 55, s. 1-8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Environmental contaminants have previously been linked to components of the Metabolic Syndrome (MetS). However, exposure to environmental contaminants is in part determined by various lifestyle factors. Objective: Using an "Environmental Wide Association Study" (ELWAS) integrating environmental contaminants and lifestyle factors, we aimed to evaluate a possible additive role of both contaminants and lifestyle factors regarding MetS. Methods: 1016 subjects aged 70 years were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. 43 environmental contaminants were measured in the circulation. Dietary records were used to evaluate 21 nutrients and the proportions of 13 fatty acids were determined in serum cholesterol esters to further quantify fat quality intake. Adding 5 other important lifestyle factors yielded together 76 environmental and lifestyle factors. MetS was defined by the NCEP/ATPIII-criteria. Results: 23% had MetS. Using cross-validation within the sample, fourteen environmental contaminants or lifestyle factors consistently showed a false discovery rate <0.05. When the major variables entered a multiple model, only p,p'-DDE levels (positive), PCB209 (inverse) and exercise habits (inverse) were together with a fatty acid pattern, with high levels of palmitic acid and oleic acid and low levels of linoleic acid, related to MetS (p<0.002 for all variables). Conclusion: Using a cross-sectional EWAS approach, certain environmental contaminants and lifestyle factors were found to be associated with prevalent metabolic syndrome in an additive fashion in an elderly population. 

  • 300.
    Lind, P. Monica
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Roos, Vendela
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Rönn, Monika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Johansson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Kullberg, Joel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Serum concentrations of phthalate metabolites are related to abdominal fat distribution two years later in elderly women2012Ingår i: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 11, nr 1, s. 21-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    Phthalates, commonly used to soften plastic goods, are known PPAR-agonists affecting lipid metabolism and adipocytes in the experimental setting. We evaluated if circulating concentrations of phthalates were related to different indices of obesity using data from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Data from both dual-energy X-ray absorptiometry (DXA) and abdominal magnetic resonance imaging (MRI) were used.

    METHODS:

    1,016 subjects aged 70 years were investigated in the PIVUS study. Four phthalate metabolites were detected in the serum of almost all subjects (> 96%) by an API 4000 liquid chromatograph/tandem mass spectrometer. Abdominal MRI was performed in a representative subsample of 287 subjects (28%), and a dual-energy X-ray absorptiometry (DXA)-scan was obtained in 890 (88%) of the subjects two year following the phthalate measurements.

    RESULTS:

    In women, circulating concentrations of mono-isobutyl phthalate (MiBP) were positively related to waist circumference, total fat mass and trunk fat mass by DXA, as well as to subcutaneous adipose tissue by MRI following adjustment for serum cholesterol and triglycerides, education, smoking and exercise habits (all p < 0.008). Mono-methyl phthalate (MMP) concentrations were related to trunk fat mass and the trunk/leg-ratio by DXA, but less powerful than MiBP. However, no such statistically significant relationships were seen in men.

    CONCLUSIONS:

    The present evaluation shows that especially the phthalate metabolite MiBP was related to increased fat amount in the subcutaneous abdominal region in women measured by DXA and MRI two years later.

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