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  • 201.
    Ardenfors, Oscar
    et al.
    Stockholm University, Faculty of Science, Department of Physics.
    Henry, Thomas
    Stockholm University, Faculty of Science, Department of Physics.
    Gudowska, Irena
    Stockholm University, Faculty of Science, Department of Physics.
    Poludniowski, Gavin
    Dasu, Alexandru
    Organ doses from a proton gantry-mounted cone-beam computed tomography system characterized with MCNP6 and GATE2018In: Physica medica (Testo stampato), ISSN 1120-1797, E-ISSN 1724-191X, Vol. 53, p. 56-61Article in journal (Refereed)
    Abstract [en]

    Purpose

    To determine organ doses from a proton gantry-mounted cone-beam computed tomography (CBCT) system using two Monte Carlo codes and to study the influence on organ doses from different acquisition modes and repeated imaging.

    Methods

    The CBCT system was characterized with MCNP6 and GATE using measurements of depth doses in water and spatial profiles in air. The beam models were validated against absolute dose measurements and used to simulate organ doses from CBCT imaging with head, thorax and pelvis protocols. Anterior and posterior 190° scans were simulated and the resulting organ doses per mAs were compared to those from 360° scans. The influence on organ doses from repeated imaging with different imaging schedules was also investigated.

    Results

    The agreement between MCNP6, GATE and measurements with regard to depth doses and beam profiles was within 4% for all protocols and the corresponding average agreement in absolute dose validation was 4%. Absorbed doses for in-field organs from 360° scans ranged between 6 and 8 mGy, 15–17 mGy and 24–54 mGy for the head, thorax and pelvis protocols, respectively. Cumulative organ doses from repeated CBCT imaging ranged between 0.04 and 0.32 Gy for weekly imaging and 0.2–1.6 Gy for daily imaging. The anterior scans resulted in an average increase in dose per mAs of 24% to the organs of interest relative to the 360° scan, while the posterior scan showed a 37% decrease.

    Conclusions

    A proton gantry-mounted CBCT system was accurately characterized with MCNP6 and GATE. Organ doses varied greatly depending on acquisition mode, favoring posterior scans.

  • 202.
    Ardenfors, Oscar
    et al.
    Stockholm University, Faculty of Science, Department of Physics. Linköping University, Sweden; Karolinska Institutet, Sweden.
    Josefsson, Dan
    Dasu, Alexandru
    Are IMRT treatments in the head and neck region increasing the risk of secondary cancers?2014In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, no 8, p. 1041-1047Article in journal (Refereed)
    Abstract [en]

    Background. Intensity-modulated radiation therapy (IMRT) has been increasingly employed for treating head and neck (H&N) tumours due to its ability to produce isodoses suitable for the complex anatomy of the region. The aim of this study was to assess possible differences between IMRT and conformal radiation therapy (CRT) with regard to risk of radiation-induced secondary malignancies for H&N tumours. Material and methods. IMRT and CRT plans were made for 10 H&N adult patients and the resulting treatment planning data were used to calculate the risk of radiation-induced malignancies in four different tissues. Three risk models with biologically relevant parameters were used for calculations. The influence of scatter radiation and repeated imaging sessions has also been investigated. Results. The results showed that the total lifetime risks of developing radiation-induced secondary malignancies from the two treatment techniques, CRT and IMRT, were comparable and in the interval 0.9-2.5%. The risk contributions from the primary beam and scatter radiation were comparable, whereas the contribution from repeated diagnostic imaging was considerably smaller. Conclusion. The results indicated that the redistribution of the dose characteristic to IMRT leads to a redistribution of the risks in individual tissues. However, the total levels of risk were similar between the two irradiation techniques considered.

  • 203. Arendt, Josephine
    et al.
    Van Someren, Eus J W
    Appleton, Richard
    Skene, Debra J
    Akerstedt, Torbjorn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Clinical update: melatonin and sleep disorders.2008In: Clin Med, ISSN 1470-2118, Vol. 8, no 4, p. 381-3Article in journal (Refereed)
    Abstract [en]

    Clinical update: melatonin and sleep disorders.

    Arendt J, Van Someren EJ, Appleton R, Skene DJ, Akerstedt T.

    Centre for Chronobiology, Faculty of Health and Medical Sciences, University of Surrey, Guildford. j.arendt@surrey.ac.uk

    The hormone melatonin is increasingly used for the treatment of certain sleep disorders, particularly those related to disturbed biological rhythms. This article summarises current knowledge of its mechanism of action and identifies situations where there is good evidence for its efficacy. The authors provide advice, based on their own experience and consistent published data, concerning the dose range of melatonin to be used and the critically important question of the timing of treatment. Anecdotal evidence for the use of melatonin needs to be replaced by data from well-controlled, preferably multi-centre, randomised clinical trials.

  • 204. Arentsen, T.
    et al.
    Qian, Y.
    Gkotzis, Spyridon
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Karolinska Institutet, Sweden.
    Femenia, T.
    Wang, T.
    Udekwu, Klas
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Forssberg, H.
    Heijtz, R. Diaz
    The bacterial peptidoglycan-sensing molecule Pglyrp2 modulates brain development and behavior2017In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 22, no 2, p. 257-266Article in journal (Refereed)
    Abstract [en]

    Recent studies have revealed that the gut microbiota modulates brain development and behavior, but the underlying mechanisms are still poorly understood. Here, we show that bacterial peptidoglycan (PGN) derived from the commensal gut microbiota can be translocated into the brain and sensed by specific pattern-recognition receptors (PRRs) of the innate immune system. Using expression-profiling techniques, we demonstrate that two families of PRRs that specifically detect PGN (that is, PGN-recognition proteins and NOD-like receptors), and the PGN transporter PepT1 are highly expressed in the developing brain during specific windows of postnatal development in both males and females. Moreover, we show that the expression of several PGN-sensing molecules and PepT1 in the developing striatum is sensitive to manipulations of the gut microbiota (that is, germ-free conditions and antibiotic treatment). Finally, we used the PGN-recognition protein 2 (Pglyrp2) knockout mice to examine the potential influence of PGN-sensing molecules on brain development and behavior. We demonstrate that the absence of Pglyrp2 leads to alterations in the expression of the autism risk gene c-Met, and sex-dependent changes in social behavior, similar to mice with manipulated microbiota. These findings suggest that the central activation of PRRs by microbial products could be one of the signaling pathways mediating the communication between the gut microbiota and the developing brain.

  • 205.
    Arko-Mensah, John
    Stockholm University, Faculty of Science, Wenner-Gren Institute for Experimental Biology.
    Immune evasion and identification of biomarkers associated with mycobacterial infection2007Licentiate thesis, comprehensive summary (Other academic)
  • 206.
    Arko-Mensah, John
    Stockholm University, Faculty of Science, Wenner-Gren Institute for Experimental Biology.
    Mycobacterial infection: Immune evasion, host susceptibility and immunological markers of diagnostic importance2008Doctoral thesis, monograph (Other academic)
    Abstract [en]

    IIn the first study, we investigated the functional implications of prolonged TLR signalling on IFN-γ mediated killing of mycobacteria by murine macrophages in vitro. TLR2, but not TLR4 ligation interfered with IFN-γ mediated killing of mycobacteria in macrophages. In terms of mechanisms, neither TNF nor nitric oxide (NO) production was significantly affected, and the refractoriness induced could be reversed with increasing amounts of IFN-γ In the second study, we aimed to identify immunological markers of diagnostic importance in both the respiratory tract and serum during pulmonary mycobacterial infection in mice. We found that increased levels of immunological markers in the respiratory tract, but not serum, correlated better with active mycobacterial infection in the lungs, suggesting that the immune response in the respiratory tract is more reflective of the infection status and pathology than the systemic response. Finally, we investigated the level and nature of immune responses to pulmonary mycobacterial infection in BALB/c and C57BL/6 mice, two mouse strains known to exhibit different susceptibilities to infection with several intracellular pathogens, including mycobacteria. We showed that increased susceptibility of BALB/c mice to early mycobacterial infection was associated with reduced Th1 immune responses, and increased sTNFR secretion in the lung. Moreover, BALB/c mice recruited fewer monocytes/macrophages to the lung, and although IFN-γ stimulation of infected bone marrow derived macrophages in both mouse strains resulted in induction of antimycobacterial activity, BALB/c mice had a reduced capacity to kill ingested bacteria. The work presented in this thesis provide further insight into the mechanisms involved in the host-pathogen interaction; from persistence, to the immunological processes induced by the pathogen, to susceptibility of the host to infection.

  • 207. Arko-Mensah, John
    et al.
    Rahman, Muhammad Jubayer
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Julián, Eshter
    Horner, Gudron
    Singh, Mahavir
    Fernández, Carmen
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Increased levels of immunological markers in the respiratory tract but not in serum correlate with active pulmonary mycobacterial infection in mice2009In: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 15, no 8, p. 777-786Article in journal (Refereed)
    Abstract [en]

    Immunological tests for the diagnosis of tuberculosis (TB) have relied mostly on detection of immune markers in serum or release of cytokines by mononuclear cells in vitro. These tests, although useful, sometimes fail to discriminate between active infection and contact with mycobacteria or vaccination. TB is primarily a disease of the lung, and therefore identification of immunological markers in the respiratory tract will be more likely to reflect the infection status or disease activity. In this study, it is demonstrated that active infection of mice with Mycobacterium bovis bacille Calmette-Guérin (BCG), but not exposure to heat-killed BCG, induced production of interleukin-12 (IL-12), interferon-gamma (IFN-gamma) or soluble tumour necrosis factor receptors (sTNFRs) locally in the lungs, as detected in bronchoalveolar lavage (BAL) fluid. There was a strong correlation between bacterial growth in the lung and levels of sTNFRs, and to some extent IL-12 and IFN-gamma, in BAL fluid. Furthermore, sTNFR levels increased significantly in BAL fluid after reactivation of controlled infection with dexamethasone, and this correlated with increased bacterial growth in the lungs. Finally, infection, but not exposure to non-replicating mycobacteria, induced specific IgG and IgA in BAL fluid. Elevated levels of all biomarkers measured were also detected in the serum, but correlation with infection was not as clear as in the case of BAL fluid. Taken together, the detection of sTNFRs and mycobacterium-specific antibodies, especially IgA, locally in the lungs could be used as immunological markers for the diagnosis of TB.

  • 208.
    Arnberg, Filip K.
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Uppsala University, Sweden.
    Gudmundsdóttir, Ragnhildur
    Butwicka, Agnieszka
    Fang, Fang
    Lichtenstein, Paul
    Hultman, Christina M.
    Valdimarsdóttir, Unnur A.
    Psychiatric disorders and suicide attempts in Swedish survivors of the 2004 southeast Asia tsunami: a 5 year matched cohort study2015In: Lancet psychiatry, ISSN 2215-0374, E-ISSN 2215-0366, Vol. 2, no 9, p. 817-824Article in journal (Refereed)
    Abstract [en]

    Background: Survivors of natural disasters are thought to be at an increased risk of psychiatric disorders, however the extent of this risk, and whether it is linked to pre-existing psychopathology, is not known. We aimed to establish whether Swedish survivors of tsunamis from the 2004 Sumatra-Andaman earthquake had increased risks of psychiatric disorders and suicide attempts 5 years after repatriation.

    Methods: We identified Swedish survivors repatriated from southeast Asia (8762 adults and 3742 children) and 864 088 unexposed adults and 320 828 unexposed children matched for sex, age, and socioeconomic status. We retrieved psychiatric diagnoses and suicide attempts from the Swedish patient register for the 5 years after the tsunami (from Dec 26, 2004, to Jan 31, 2010) and estimated hazard ratios (HRs), then adjusted for pre-tsunami psychiatric disorders, and, for children, for parental pre-tsunami disorders.

    Findings: Exposed adults were more likely than unexposed adults to receive any psychiatric diagnosis (547 [6.2%] vs 47 734 [5.5%]; adjusted HR 1.21, 95% CI 1.11-1.32), particularly stress-related disorders (187 [2.1%] vs 8831 [1.0%]; 2.27, 1.96-2.62) and suicide attempts (38 [0.43%] vs 2752 [0.32%]; 1.54, 1.11-2.13), but not mood or anxiety disorders. Risk of psychiatric diagnoses did not differ between exposed and unexposed children and adolescents (248 [6.6] vs 22 081 [6.9%]; 0.98, 0.86-1.11), although exposed children and adolescents had a higher risk for suicide attempts with uncertain intent (1.43; 1.01-2.02) and stress-related disorders (1.79; 1.30-2.46), mainly during the first 3 months after the tsunami.

    Interpretation: The 2004 tsunami was, independently of previous psychiatric morbidity, associated with an increased risk of severe psychopathology, mainly stress-related disorders and suicide attempts, in children and adults. Survivors of natural disasters should be targeted with early interventions and active long-term follow-up to prevent, detect, and alleviate psychiatric disorders that might follow.

    Funding: The Swedish Council for Working Life and Social Research, Swedish Board of Health and Welfare, Polish Ministry of Science and Higher Education, Swedish Society for Medical Research.

  • 209.
    Arnberg, Filip K.
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Uppsala University, Sweden.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Morey, Jennifer N.
    Segerström, Suzanne C.
    Self-rated health and interleukin-6: Longitudinal relationships in older adults2016In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 54, p. 226-232Article in journal (Refereed)
    Abstract [en]

    Background: Both self-rated health (SRH) and inflammation are implicated in chronic diseases and premature mortality. Better SRH is associated with lower proinflammatory cytokines, but there is little evidence about whether this relationship is more stable or dynamic.

    Objective: To study the between- and within-person associations between SRH and IL-6.

    Methods: Older adults (N=131; Mage=75years) rated their health and provided blood samples for analysis of IL-6 at separate occasions every 6months over a period up to 5years. Age, sex, BMI, neuroticism, and statin use were examined as covariates in multilevel models.

    Results: In bivariate models, better SRH, lower BMI, younger age, and female sex correlated with lower IL-6. In multilevel models, stable SRH (between-person differences; p<.001) but not dynamic SRH (within-person changes; p=.93) correlated with IL-6. The stable relationship persisted with demographic and health covariates in the model.

    Conclusions: Better stable SRH but not dynamic SRH was robustly associated with lower IL-6 among older adults, lending support to previous cross-sectional findings on the relation between inflammatory markers and SRH. The findings suggest that trait-like mechanisms, rather than changes over a time scale of 6-month waves, govern this association. To further investigate the mechanisms behind the SRH-IL-6 association, studies with different measurement frequencies, higher within-person variability, and experimental approaches are warranted.

  • 210.
    Arnberg, Filip K.
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Uppsala University, Sweden.
    Michel, Per-Olof
    Lundin, Tom
    Posttraumatic stress in survivors 1 month to 19 years after an airliner emergency landing2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 3, article id e0119732Article in journal (Refereed)
    Abstract [en]

    Posttraumatic stress (PTS) is common in survivors from life-threatening events. Little is known, however, about the course of PTS after life threat in the absence of collateral stressors (e.g., bereavement, social stigma, property loss) and there is a scarcity of studies about PTS in the long term. This study assessed the short- and long-term course of PTS, and the influence of gender, education and age on the level and course of PTS, in survivors from a non-fatal airliner emergency landing caused by engine failure at an altitude of 1 km. There were 129 persons on board. A survey including the Impact of Event Scale was distributed to 106 subjects after 1 month, 4 months, 14 months, and 25 months, and to 95 subjects after 19 years (response rates 64-83%). There were initially high levels of PTS. The majority of changes in PTS occurred from 1 to 4 months after the event. There were small changes from 4 to 25 months but further decrease in PTS thereafter. Female gender was associated with higher levels of PTS whereas gender was unrelated to the slope of the short- and long-term trajectories. Higher education was related to a quicker recovery although not to initial or long-term PTS. Age was not associated with PTS. The present findings suggest that a life-threatening experience without collateral stressors may produce high levels of acute posttraumatic stress, yet with a benign prognosis. The findings further implicate that gender is unrelated to trajectories of recovery in the context of highly similar exposure and few collateral stressors.

  • 211. Arnetz, Bengt
    et al.
    Frenzel, Lena
    Åkerstedt, Torbjörn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Lisspers, Jan
    The brief fatigue syndrome scale: Validation and utilization in fatigue recovery studies2008In: Fatigue Science for Human Health, Springer , 2008, p. 55-66Chapter in book (Other academic)
  • 212.
    Aronsson, Gunnar
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Astvik, Wanja
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Mälardalen University, Sweden.
    Gustafsson, Klas
    Work conditions, Recovery and Health: A study among workers within Pre-School, Home Care and Social Work2014In: British Journal of Social Work, ISSN 0045-3102, E-ISSN 1468-263X, Vol. 44, no 6, p. 1654-1672Article in journal (Refereed)
    Abstract [en]

    The study investigated the working conditions associated with the accumulation of stress and lack of recovery and how recovery is related to health. The study group was employed in pre-school, home care and social work (n = 193). Recovery was assumed to be an explanatory variable for the relations between work and health. The response rate on a survey was 79 per cent. Cluster analysis identified three groups: the ‘Recovered’ (36 per cent of the total group) and ‘Not Recovered’ (25 per cent) and the ‘In-between’ (39 per cent). The Not Recovered displayed the whole chain of risk factors, involving difficult working conditions to which they responded with increased compensatory strategies. Despite this group having significantly greater reports of ill health, work absenteeism was not greater, which is likely related to their substituting sickness absence with sickness presence. As many as 43 per cent of the social workers were found to belong to the Not Recovered group. Multiple regression analyses controlling for background variables revealed that the Not Recovered group had a significantly higher relative risk for poor self-rated health than those in the Recovered group. Even sharper increases in relative risk existed for the other five symptoms that were analysed. Practical implications and new research questions are discussed.

  • 213.
    Aronsson, Gunnar
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Work and organizational psychology.
    Nylén, Eva Charlotta
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Work and organizational psychology.
    Ishall, Lars
    Lindfors, Petra
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Work and organizational psychology.
    Sverke, Magnus
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Work and organizational psychology. North-West University, Vanderbijlpark, South Africa.
    The long arm of the job - work characteristics and recovery windows in social welfare work2019In: International Journal of Workplace Health Management, ISSN 1753-8351, E-ISSN 1753-836X, Vol. 12, no 1, p. 15-27Article in journal (Refereed)
    Abstract [en]

    Purpose Social welfare work contains elements that may be difficult for employees to put out of their minds when the working day ends, which may affect the recovery. The purpose of this paper is to analyze the length of recovery in relation to different work characteristics and to two types of welfare work. Design/methodology/approach All 1,365 employees, excluding managers, of two municipality administrations were invited to a survey study. Of these, 673 (49 percent) responded. After adjusting for partial missing, the effective sample included 580 employees (43 percent). Retrospective ratings of four recovery windows were analyzed: recovery after one night's sleep, weekends, shorter holidays and vacations. Findings Employees with a university education were less recovered than those with a shorter education. For those with a university education, the long arm of the job mainly involved failures regarding qualitative job demands (task difficulty). For those with a shorter education, quantitative job demands (too much to do) were most prominent for their prolonged recovery. Feedback from managers had consistent and positive associations with all four recovery windows among employees with a university education, but not among those with a shorter education for whom instead having too much to do and social support had significant spillover effects. Originality/value The identified differences may relate to employees with a university education having more problem-solving tasks, which may result in a higher need of work-related feedback but also in difficulties detaching from work. Thus, education and job characteristics have differential associations with self-rated recovery.

  • 214.
    Aronsson, Gunnar
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Work and organizational psychology.
    Theorell, Töres
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Grape, Tom
    Hammarström, Anne
    Hogstedt, Christer
    Marteinsdottir, Ina
    Skoog, Ingmar
    Träskman-Bendz, Lil
    Hall, Charlotte
    A systematic review including meta-analysis of work environment and burnout symptoms2017In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 17, no 1, article id 264Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Practitioners and decision makers in the medical and insurance systems need knowledge on the relationship between work exposures and burnout. Many burnout studies - original as well as reviews - restricted their analyses to emotional exhaustion or did not report results on cynicism, personal accomplishment or global burnout. To meet this need we carried out this review and meta-analyses with the aim to provide systematically graded evidence for associations between working conditions and near-future development of burnout symptoms.

    METHODS: A wide range of work exposure factors was screened. Inclusion criteria were: 1) Study performed in Europe, North America, Australia and New Zealand 1990-2013. 2) Prospective or comparable case control design. 3) Assessments of exposure (work) and outcome at baseline and at least once again during follow up 1-5 years later. Twenty-five articles met the predefined relevance and quality criteria. The GRADE-system with its 4-grade evidence scale was used.

    RESULTS: Most of the 25 studies focused emotional exhaustion, fewer cynicism and still fewer personal accomplishment. Moderately strong evidence (grade 3) was concluded for the association between job control and reduced emotional exhaustion and between low workplace support and increased emotional exhaustion. Limited evidence (grade 2) was found for the associations between workplace justice, demands, high work load, low reward, low supervisor support, low co-worker support, job insecurity and change in emotional exhaustion. Cynicism was associated with most of these work factors. Reduced personal accomplishment was only associated with low reward. There were few prospective studies with sufficient quality on adverse chemical, biological and physical factors and burnout.

    CONCLUSION: While high levels of job support and workplace justice were protective for emotional exhaustion, high demands, low job control, high work load, low reward and job insecurity increased the risk for developing exhaustion. Our approach with a wide range of work exposure factors analysed in relation to the separate dimensions of burnout expanded the knowledge of associations, evidence as well as research needs. The potential of organizational interventions is illustrated by the findings that burnout symptoms are strongly influenced by structural factors such as job demands, support and the possibility to exert control.

  • 215.
    Aronsson, Vanda
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Health differences between employees in human service professions and other professions: The impact of psychosocial and organizational work environment2016Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    While recent publications indicate that employees in human service professions have higher risk of sickness absence and mental ill-health, little is known about the association with other health outcomes and possible mechanisms behind the differential risk. This study investigates differences in burnout, self-rated health and sickness absence between those in human service professions and other professions and examines whether differences in psychosocial and organizational work environment can explain possible variations. Data were derived from the Swedish Longitudinal Occupational Survey of Health (SLOSH), an approximately representative sample of the Swedish working population (n=4486). Results from binary logistic regressions suggested that those in human service professions had higher odds of burnout and sickness absence those in other professions. Differences in burnout were explained by background variables while differences in sickness absence were explained by psychosocial and organizational work factors. Employees in human service professions had lower odds of suboptimal self-rated health than others in the fully adjusted model. Women were at higher risk of burnout, sickness absence, and all adverse psychosocial and organizational work environment factors except social support. Future studies should investigate the most crucial psychosocial and organizational work factors in human service professions with the objective to improve employee health.  

  • 216.
    Aronsson, Vanda
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Stockholm University, Faculty of Social Sciences, Department of Public Health Sciences.
    Toivanen, Susanna
    Stockholm University, Faculty of Social Sciences, Department of Public Health Sciences. Mälardalen University, Sweden.
    Leineweber, Constanze
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Nyberg, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Can a poor psychosocial work environment and insufficient organizational resources explain the higher risk of ill-health and sickness absence in human service occupations? Evidence from a Swedish national cohort2019In: Scandinavian Journal of Public Health, ISSN 1403-4948, E-ISSN 1651-1905, Vol. 47, no 3, p. 310-317Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of this study was to investigate differences in burnout, self-rated health (SRH) and sickness absence between human service occupations (HSOs) and other occupations, and whether they can be attributed to differences in psychosocial work environment and organizational resources. Methods: Data were derived from the Swedish Longitudinal Occupational Survey of Health, an approximately representative sample of the Swedish working population (n = 4408). Employment in HSOs, psychosocial work environment and organizational resources in 2012 predicted relative risks of sickness absence, burnout and suboptimal SRH in 2014 using modified Poisson regressions. The psychosocial work factors' and organizational resource variables' relative importance were estimated by adding them to the models one by one, and with population attributable fractions (PAFs). Results: Employment in HSOs was associated with a higher risk of sickness absence and the risk was explained by psychosocial and organizational factors, particularly high emotional demands, low work-time control and exposure to workplace violence. Employment in HSOs was not associated with burnout after sociodemographic factors were adjusted for, and furthermore not with SRH. A lower risk of suboptimal SRH was found in HSOs than in other occupations with equivalent psychosocial work environment and organizational resources. PAFs indicated that psychosocial work environment and organizational resource improvements could lead to morbidity reductions for all outcomes; emotional demands were more important in HSOs. Conclusions: HSOs had higher risks of sickness absence and burnout than other occupations. The most important work factors to address were high emotional demands, low work-time control, and exposure to workplace violence.

  • 217.
    Arrighi, Romanico B. G.
    et al.
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Ebikeme, Charles
    Jiang, Yang
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Ranford-Cartwright, Lisa
    Barrett, Michael P.
    Langel, Ülo
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Faye, Ingrid
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Cell-penetrating peptide TP10 shows broad-spectrum activity against both Plasmodium falciparum and Trypanosoma brucei brucei2008In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 52, no 9, p. 3414-3417Article in journal (Refereed)
    Abstract [en]

    Malaria and trypanosomiasis are diseases which afflict millions and for which novel therapies are urgently required. We have tested two well-characterized cell-penetrating peptides (CPPs) for antiparasitic activity. One CPP, designated TP10, has broad-spectrum antiparasitic activity against Plasmodium falciparum, both blood and mosquito stages, and against blood-stage Trypanosoma brucei brucei.

  • 218.
    Arshamian, Artin
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Perception and psychophysics. Karolinska Institutet, Sweden; Donders Institute for Brain, Cognition, and Behavior, The Netherlands; Radboud University, The Netherlands.
    Iravani, Behzad
    Majid, Asifa
    Lundström, Johan N.
    Respiration Modulates Olfactory Memory Consolidation in Humans2018In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 38, no 48, p. 10286-10294Article in journal (Refereed)
    Abstract [en]

    In mammals respiratory-locked hippocampal rhythms are implicated in the scaffolding and transfer of information between sensory and memory networks. These oscillations are entrained by nasal respiration and driven by the olfactory bulb. They then travel to the piriform cortex where they propagate further downstream to the hippocampus and modulate neural processes critical for memory formation. In humans, bypassing nasal airflow through mouth-breathing abolishes these rhythms and impacts encoding as well as recognition processes thereby reducing memory performance. It has been hypothesized that similar behavior should be observed for the consolidation process, the stage between encoding and recognition, were memory is reactivated and strengthened. However, direct evidence for such an effect is lacking in human and nonhuman animals. Here we tested this hypothesis by examining the effect of respiration on consolidation of episodic odor memory. In two separate sessions, female and male participants encoded odors followed by a 1 h awake resting consolidation phase where they either breathed solely through their nose or mouth. Immediately after the consolidation phase, memory for odors was tested. Recognition memory significantly increased during nasal respiration compared with mouth respiration during consolidation. These results provide the first evidence that respiration directly impacts consolidation of episodic events, and lends further support to the notion that core cognitive functions are modulated by the respiratory cycle.

  • 219. Asberg, Marie
    et al.
    Nygren, Ake
    Leopardi, Rosario
    Rylander, Gunnar
    Peterson, Ulla
    Wilczek, Lukas
    Källmén, Håkan
    Ekstedt, Mirjam
    Akerstedt, Torbjörn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Lekander, Mats
    Ekman, Rolf
    Novel biochemical markers of psychosocial stress in women.2009In: PLoS ONE, ISSN 1932-6203, Vol. 4, no 1, p. e3590-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Prolonged psychosocial stress is a condition assessed through self-reports. Here we aimed to identify biochemical markers for screening and early intervention in women. METHODS: Plasma concentrations of interleukin (IL) 1-alpha, IL1-beta, IL-2, IL-4, IL-6, IL-8, IL-10, interferon-gamma (INF-gamma), tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), thyroid stimulating hormone (TSH), total tri-iodothyronine (TT3), total thyroxine (TT4), prolactin, and testosterone were measured in: 195 women on long-term sick-leave for a stress-related affective disorder, 45 women at risk for professional burnout, and 84 healthy women. RESULTS: We found significantly increased levels of MCP-1, VEGF and EGF in women exposed to prolonged psychosocial stress. Statistical analysis indicates that they independently associate with a significant risk for being classified as ill. CONCLUSIONS: MCP-1, EGF, and VEGF are potential markers for screening and early intervention in women under prolonged psychosocial stress.

  • 220.
    Asgard, Rikard
    et al.
    Uppsala Univ, Dept Pharmaceut Biosci., Uppsala, Sweden.
    Haghdoost, Siamak
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Golkar, Siv Osterman
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Hellman, Bjorn
    Uppsala Univ, Dept Pharmaceut Biosci., Uppsala, Sweden.
    Czene, Stefan
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Evidence for different mechanisms of action behind the mutagenic effects of 4-NOPD and OPD: the role of DNA damage, oxidative stress and an imbalanced nucleotide pool2013In: Mutagenesis, ISSN 0267-8357, E-ISSN 1464-3804, Vol. 28, no 6, p. 637-644Article in journal (Refereed)
    Abstract [en]

    The mutagenicity of 4-nitro-o-phenylenediamine (4-NOPD) and o-phenylenediamine (OPD) was compared using the Mouse Lymphoma Assay (MLA) with or without metabolic activation (S9). As expected, OPD was found to be a more potent mutagen than 4-NOPD. To evaluate possible mechanisms behind their mutagenic effects, the following end points were also monitored in cells that had been exposed to similar concentrations of the compounds as in the MLA: general DNA damage (using a standard protocol for the Comet assay); oxidative DNA damage (using a modified procedure for the Comet assay in combination with the enzyme hOGG1); reactive oxygen species (ROS; using the CM-H(2)DCFDA assay); and the balance of the nucleotide pool (measured after conversion to the corresponding nucleosides dC, dT, dG and dA using high-performance liquid chromatography). Both compounds increased the level of general DNA damage. Again, OPD was found to be more potent than 4-NOPD (which only increased the level of general DNA damage in the presence of S9). Although less obvious for OPD, both compounds increased the level of oxidative DNA damage. However, an increase in intracellular ROS was only observed in cells exposed to 4-NOPD, both with and without S9 (which in itself induced oxidative stress). Both compounds decreased the concentrations of dA, dT and dC. A striking effect of OPD was the sharp reduction of dA observed already at very low concentration, both with and without S9 (which in itself affected the precursor pool). Taken together, our results indicate that indirect effects on DNA, possibly related to an unbalanced nucleotide pool, mediate the mutagenicity and DNA-damaging effects of 4-NOPD and OPD to a large extent. Although induction of intracellular oxidative stress seems to be a possible mechanism behind the genotoxicity of 4-NOPD, this pathway seems to be of less importance for the more potent mutagen OPD.

  • 221. Ask, Lina Schollin
    et al.
    Liu, Can
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS). Karolinska Institutet, Sweden.
    Gauffin, Karl
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Hjern, Anders
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS). Sachs’ Children and Youth Hospital, South General Hospital, Sweden; Karolinska Institutet, Sweden.
    The Effect of Rotavirus Vaccine on Socioeconomic Differentials of Paediatric Care Due to Gastroenteritis in Swedish Infants2019In: International Journal of Environmental Research and Public Health, ISSN 1661-7827, E-ISSN 1660-4601, Vol. 16, no 7, article id 1095Article in journal (Refereed)
    Abstract [en]

    Background: Previous Swedish studies have shown a social gradient on paediatric care for viral gastroenteritis. Aim: To study the effect of a free rotavirus vaccine programme on hospital care for viral gastroenteritis. Method: A register-based national cohort study of paediatric in- and outpatient care for viral gastroenteritis in children <2 years old in two Swedish counties in 2014-2017, with the rest of the country as comparison. Adjusted hazard ratios were estimated by the differences-in-differences (DiD) estimator in Cox regression in the entire cohort and by social indicators. Results: Reductions of 37% and 24% for inpatient care, and 11 % and 21% for outpatient care for viral gastroenteritis were found in the Stockholm and Jonkoping counties, respectively, after adjusting for time trends and social indicators. For inpatient care, the change was similar over social groups in both counties. In the larger county of Stockholm, smaller reductions in outpatient care were detected for children in socially disadvantaged families. Conclusions: A free rotavirus vaccination programme moderately reduced paediatric care for viral gastroenteritis. There were indications of an increase in socioeconomic differences in paediatric outpatient care for viral gastroenteritis, but further studies are needed to confirm this result in a broader health care perspective.

  • 222.
    Aslam, Muhammad
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    The fruit fly Drosophila melanogaster GSTE6 and E7; characterization, immobilization and transgenic overexpression2014Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Glutathione transferases (GSTs) are multifunctional enzymes that are universally distributed in most eukaryotes and prokaryotes. They play a pivotal role in the metabolism and detoxication of numerous endogenous and exogenous electrophiles by conjugating them with ubiquitous tripeptide glutathione. In this study we have immobilized two heterologously expressed and purified Epsilon-class enzymes, GSTE6 and GSTE7, from of Drosophila melanogaster on nanoporous alumina membranes. The membranes were derivatized with 3-aminopropyl-triethoxysilane and the amino groups were activated with carbonyldiimidazole to allow coupling of the enzymes. Kinetic analyses of the immobilized enzymes were carried out in a circulating flow system using CDNB (1-chloro-2,4-dinitrobenzene) as substrate, followed by specificity screening with alternative substrates. A good correlation was observed between the substrate screening data for immobilized enzyme and corresponding data for the enzymes in solution. The stability of the immobilized enzymes was virtually identical to that for the enzymes in solution and no leakage of enzyme from the matrix could be observed.

    Additionally, we have investigated the catalytic activities of GSTE7 with organic isothiocyanates (ITCs). These reactive compounds are strong electrophilic molecules produced in plants by the hydrolysis of glucosinolates and exert toxicity in biological tissues.  Our in vitro studies, showed high catalytic activity of GSTE7 towards ITCs. We have then explored the in vivo effect of phenethyl isothiocyanate (PEITC) and allyl isothiocyanate (AITC) in transgenic fruit flies overexpressing GSTE7. A concentration of 0.25 mM PEITC in standard fly food was shown to be toxic to flies and significantly shortened the lifespan. We noticed that overexpression of GSTE7 could protect females from the initial acute toxic effects, but had no positive effect on long term exposure. The effect on males seems to be the opposite to that of females, where a higher mortality was seen in fly males overexpressing GST E7 after one week of exposure.  On the other hand 1mM concentration of AITC showed no toxic effects, but dramatically reduced the oviposition activity of wild-type flies in comparison to the transgenic flies.

  • 223.
    Aslam, Muhammad
    et al.
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Dahlberg, Olle
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Mannervik, Bengt
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Mannervik, Mattias
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Transgenic Overexpression of Glutathione Transferase E7 in Drosophila Attenuates Toxicity of Organic Isothiocyanates Affecting Survival and OvipositionManuscript (preprint) (Other academic)
    Abstract [en]

    Organic isothiocyanates (ITCs) are allelochemicals produced by plants in order to combat insects and other herbivores. The compounds are toxic electrophiles that can be inactivated and conjugated with intracellular glutathione in reactions catalyzed by glutathione transferases (GSTs). The Drosophila melanogaster GSTE7 was heterologously expressed in Escherichia coli and purified for functional studies. The enzyme showed high catalytic activity with various isothiocyanates including phenethyl isothiocyanate (PEITC) and allyl isothiocyanate (AITC), which in millimolar dietary concentrations conferred toxicity to adult D. melanogaster leading to death or a shortened life-span of the flies. In situ hybridization revealed a maternal contribution of GSTE7 transcripts to embryos, and strongest zygotic expression in the digestive tract.  Transgenesis involving the GSTE7 gene controlled by an actin promoter produced viable flies expressing the GSTE7 transcript ubiquitously. Transgenic females show a significant extension in life-span when subjected to the same PEITC treatment as the wild-type flies. By contrast, transgenic male flies showed no significant effect in the first few days, and subsequently showed a somewhat lower survival rate. At 1 mM AITC concentration, no toxicity was noted. However, the oviposition activity was dramatically enhanced from a very low level in wild-type flies reared in the presence of 1 mM AITC to values an order of magnitude higher for the transgenic flies. The results demonstrate a clear protective effect of GSTE7 against exposure to ITC allelochemicals which can affect both life-span and fecundity of female flies.

  • 224. Asmat, Tauseef M.
    et al.
    Tenenbaum, Tobias
    Jonsson, Ann-Beth
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Schwerk, Christian
    Schroten, Horst
    Impact of Calcium Signaling during Infection of Neisseria meningitidis to Human Brain Microvascular Endothelial Cells2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 12, p. e114474-Article in journal (Refereed)
    Abstract [en]

    The pili and outer membrane proteins of Neisseria meningitidis (meningococci) facilitate bacterial adhesion and invasion into host cells. In this context expression of meningococcal PilC1 protein has been reported to play a crucial role. Intracellular calcium mobilization has been implicated as an important signaling event during internalization of several bacterial pathogens. Here we employed time lapse calcium-imaging and demonstrated that PilC1 of meningococci triggered a significant increase in cytoplasmic calcium in human brain microvascular endothelial cells, whereas PilC1-deficient meningococci could not initiate this signaling process. The increase in cytosolic calcium in response to PilC1-expressing meningococci was due to efflux of calcium from host intracellular stores as demonstrated by using 2-APB, which inhibits the release of calcium from the endoplasmic reticulum. Moreover, pre-treatment of host cells with U73122 (phospholipase C inhibitor) abolished the cytosolic calcium increase caused by PilC1-expressing meningococci demonstrating that active phospholipase C (PLC) is required to induce calcium transients in host cells. Furthermore, the role of cytosolic calcium on meningococcal adherence and internalization was documented by gentamicin protection assay and double immunofluorescence (DIF) staining. Results indicated that chelation of intracellular calcium by using BAPTA-AM significantly impaired PilC1-mediated meningococcal adherence to and invasion into host endothelial cells. However, buffering of extracellular calcium by BAPTA or EGTA demonstrated no significant effect on meningococcal adherence to and invasion into host cells. Taken together, these results indicate that meningococci induce calcium release from intracellular stores of host endothelial cells via PilC1 and cytoplasmic calcium concentrations play a critical role during PilC1 mediated meningococcal adherence to and subsequent invasion into host endothelial cells.

  • 225. Asperholm, Martin
    et al.
    Nagar, Sanket
    Dekhtyar, Serhiy
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Herlitz, Agneta
    The magnitude of sex differences in verbal episodic memory increases with social progress: Data from 54 countries across 40 years2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 4, article id e0214945Article in journal (Refereed)
    Abstract [en]

    Sex differences in episodic memory have been reported. We investigate (1) the existence of sex differences in verbal and other episodic memory tasks in 54 countries, and (2) the association between the time-and country-specific social progress indicators (a) female to male ratio in education and labor force participation, (b) population education and employment, and (c) GDP per capita, and magnitude of sex differences in verbal episodic memory tasks. Data were retrieved from 612 studies, published 1973-2013. Results showed that females outperformed (Cohen's d > 0) males in verbal (42 out of 45 countries) and other (28 out of 45 countries) episodic memory tasks. Although all three social progress indicators were, separately, positively associated with the female advantage in verbal episodic memory performance, only population education and employment remained significant when considering the social indicators together. Results suggest that women's verbal episodic memory performance benefits more than men's from education and employment.

  • 226. Assadi, Ghazaleh
    et al.
    Vesterlund, Liselotte
    Bonfiglio, Ferdinando
    Mazzurana, Luca
    Cordeddu, Lina
    Schepis, Danika
    Mjösberg, Jenny
    Ruhrmann, Sabrina
    Fabbri, Alessia
    Vukojevic, Vladana
    Percipalle, Piergiorgio
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. New York University Abu Dhabi, United Arab Emirates.
    Salomons, Florian A.
    Laurencikiene, Jurga
    Törkvist, Leif
    Halfvarson, Jonas
    D'Amato, Mauro
    Functional Analyses of the Crohn's Disease Risk Gene LACC12016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 12, article id e0168276Article in journal (Refereed)
    Abstract [en]

    Background Genetic variation in the Laccase (multicopper oxidoreductase) domain-containing 1 (LACC1) gene has been shown to affect the risk of Crohn's disease, leprosy and, more recently, ulcerative colitis and juvenile idiopathic arthritis. LACC1 function appears to promote fatty-acid oxidation, with concomitant inflammasome activation, reactive oxygen species production, and anti-bacterial responses in macrophages. We sought to contribute to elucidating LACC1 biological function by extensive characterization of its expression in human tissues and cells, and through preliminary analyses of the regulatory mechanisms driving such expression. Methods We implemented Western blot, quantitative real-time PCR, immunofluorescence microscopy, and flow cytometry analyses to investigate fatty acid metabolism-immune nexus (FAMIN; the LACC1 encoded protein) expression in subcellular compartments, cell lines and relevant human tissues. Gene-set enrichment analyses were performed to initially investigate modulatory mechanisms of LACC1 expression. A small-interference RNA knockdown in vitro model system was used to study the effect of FAMIN depletion on peroxisome function. Results FAMIN expression was detected in macrophage-differentiated THP-1 cells and several human tissues, being highest in neutrophils, monocytes/macrophages, myeloid and plasmacytoid dendritic cells among peripheral blood cells. Subcellular co-localization was exclusively confined to peroxisomes, with some additional positivity for organelle endomembrane structures. LACC1 co-expression signatures were enriched for genes involved in peroxisome proliferator-activated receptors (PPAR) signaling pathways, and PPAR ligands downregulated FAMIN expression in in vitro model systems. Conclusion FAMIN is a peroxisome-associated protein with primary role(s) in macrophages and other immune cells, where its metabolic functions may be modulated by PPAR signaling events. However, the precise molecular mechanisms through which FAMIN exerts its biological effects in immune cells remain to be elucidated.

  • 227. Astaraki, Mehdi
    et al.
    Wang, Chunliang
    Buizza, Giulia
    Toma-Dasu, Iuliana
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet, Sweden.
    Lazzeroni, Marta
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet, Sweden.
    Smedby, Örjan
    Early survival prediction in non-small cell lung cancer from PET/CT images using an intra-tumor partitioning method2019In: Physica medica (Testo stampato), ISSN 1120-1797, E-ISSN 1724-191X, Vol. 60, p. 58-65Article in journal (Refereed)
    Abstract [en]

    Purpose

    To explore prognostic and predictive values of a novel quantitative feature set describing intra-tumor heterogeneity in patients with lung cancer treated with concurrent and sequential chemoradiotherapy.

    Methods

    Longitudinal PET-CT images of 30 patients with non-small cell lung cancer were analysed. To describe tumor cell heterogeneity, the tumors were partitioned into one to ten concentric regions depending on their sizes, and, for each region, the change in average intensity between the two scans was calculated for PET and CT images separately to form the proposed feature set. To validate the prognostic value of the proposed method, radiomics analysis was performed and a combination of the proposed novel feature set and the classic radiomic features was evaluated. A feature selection algorithm was utilized to identify the optimal features, and a linear support vector machine was trained for the task of overall survival prediction in terms of area under the receiver operating characteristic curve (AUROC).

    Results

    The proposed novel feature set was found to be prognostic and even outperformed the radiomics approach with a significant difference (AUROCSALoP = 0.90 vs. AUROCradiomic = 0.71) when feature selection was not employed, whereas with feature selection, a combination of the novel feature set and radiomics led to the highest prognostic values.

    Conclusion

    A novel feature set designed for capturing intra-tumor heterogeneity was introduced. Judging by their prognostic power, the proposed features have a promising potential for early survival prediction.

  • 228. Athanasiu, Lavinia
    et al.
    Giddaluru, Sudheer
    Fernandes, Carla
    Christoforou, Andrea
    Reinvang, Ivar
    Lundervold, Astri J.
    Nilsson, Lars-Göran
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Umeå University, Sweden.
    Kauppi, Karolina
    Adolfsson, Rolf
    Eriksson, Elias
    Sundet, Kjetil
    Djurovic, Srdjan
    Espeseth, Thomas
    Nyberg, Lars
    Steen, Vidar M.
    Andreassen, Ole A.
    Le Hellard, Stephanie
    A genetic association study of CSMD1 and CSMD2 with cognitive function2017In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 61, p. 209-216Article in journal (Refereed)
    Abstract [en]

    The complement cascade plays a role in synaptic pruning and synaptic plasticity, which seem to be involved in cognitive functions and psychiatric disorders. Genetic variants in the closely related CSMD1 and CSMD2 genes, which are implicated in complement regulation, are associated with schizophrenia. Since patients with schizophrenia often show cognitive impairments, we tested whether variants in CSMD1 and CSMD2 are also associated with cognitive functions per se. We took a discovery-replication approach, using well-characterized Scandinavian cohorts. A total of 1637 SNPs in CSMD1 and 206 SNPs in CSMD2 were tested for association with cognitive functions in the NCNG sample (Norwegian Cognitive NeuroGenetics; n = 670). Replication testing of SNPs with p-value < 0.001 (7 in CSMD1 and 3 in CSMD2) was carried out in the TOP sample (Thematically Organized Psychosis; n =1025) and the BETULA sample (Betula Longitudinal Study on aging, memory and dementia; n = 1742). Finally, we conducted a meta-analysis of these SNPs using all three samples. The previously identified schizophrenia marker in CSMD1 (SNP rs10503253) was also included. The strongest association was observed between the CSMDI SNP rs2740931 and performance in immediate episodic memory (p-value = 5 Chi 10(-6), minor allele A, MAF 0.48-0.49, negative direction of effect). This association reached the study-wide significance level (p <= 1.2 Chi 10(-5)). SNP rs10503253 was not significantly associated with cognitive functions in our samples. In conclusion, we studied n = 3437 individuals and found evidence that a variant in CSMD1 is associated with cognitive function. Additional studies of larger samples with cognitive phenotypes will be needed to further clarify the role of CSMD1 in cognitive phenotypes in health and disease.

  • 229. Athlin, A. Muntlin
    et al.
    Farrokhnia, N.
    von Thiele Schwarz, Ulrica
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Karolinska Institutet, Sweden.
    Introduction of multi-professional teamwork: a promising approach towards a more patient-centred care in the emergency department2014In: International Emergency Nursing, ISSN 1755-599X, E-ISSN 1878-013X, Vol. 22, no 4, p. 274-275Article in journal (Other academic)
  • 230. Atkinson, Jo-An
    et al.
    Knowles, Dylan
    Wiggers, John
    Livingston, Michael
    Room, Robin
    Stockholm University, Faculty of Social Sciences, Centre for Social Research on Alcohol and Drugs (SoRAD). La Trobe University, Australia.
    Prodan, Ante
    McDonnell, Geoff
    O'Donnell, Eloise
    Jones, Sandra
    Haber, Paul S.
    Muscatello, David
    Ezard, Nadine
    Phung, Nghi
    Freebairn, Louise
    Indig, Devon
    Rychetnik, Lucie
    Ananthapavan, Jaithri
    Wutzke, Sonia
    Harnessing advances in computer simulation to inform policy and planning to reduce alcohol-related harms2018In: International Journal of Public Health, ISSN 1661-8556, E-ISSN 1661-8564, Vol. 63, no 4, p. 537-546Article in journal (Refereed)
    Abstract [en]

    Alcohol misuse is a complex systemic problem. The aim of this study was to explore the feasibility of using a transparent and participatory agent-based modelling approach to develop a robust decision support tool to test alcohol policy scenarios before they are implemented in the real world. A consortium of Australia's leading alcohol experts was engaged to collaboratively develop an agent-based model of alcohol consumption behaviour and related harms. As a case study, four policy scenarios were examined. A 19.5 +/- 2.5% reduction in acute alcohol-related harms was estimated with the implementation of a 3 a.m. licensed venue closing time plus 1 a.m. lockout; and a 9 +/- 2.6% reduction in incidence was estimated with expansion of treatment services to reach 20% of heavy drinkers. Combining the two scenarios produced a 33.3 +/- 2.7% reduction in the incidence of acute alcohol-related harms, suggesting a synergistic effect. This study demonstrates the feasibility of participatory development of a contextually relevant computer simulation model of alcohol-related harms and highlights the value of the approach in identifying potential policy responses that best leverage limited resources.

  • 231. Atkinson, Jo-An
    et al.
    Prodan, Ante
    Livingston, Michael
    Knowles, Dylan
    O'Donnell, Eloise
    Room, Robin
    La Trobe University, Australia.
    Indig, Devon
    Page, Andrew
    McDonnell, Geoff
    Wiggers, John
    Impacts of licensed premises trading hour policies on alcohol-related harms2018In: Addiction, ISSN 0965-2140, E-ISSN 1360-0443, Vol. 113, no 7, p. 1244-1251Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIM: Evaluations of alcohol policy changes demonstrate that restriction of trading hours of both 'on'- and 'off'-licence venues can be an effective means of reducing rates of alcohol-related harm. Despite this, the effects of different trading hour policy options over time, accounting for different contexts and demographic characteristics, and the common co-occurrence of other harm reduction strategies in trading hour policy initiatives, are difficult to estimate. The aim of this study was to use dynamic simulation modelling to compare estimated impacts over time of a range of trading hour policy options on various indicators of acute alcohol-related harm.

    METHODS: An agent-based model of alcohol consumption in New South Wales, Australia was developed using existing research evidence, analysis of available data and a structured approach to incorporating expert opinion. Five policy scenarios were simulated, including restrictions to trading hours of on-licence venues and extensions to trading hours of bottle shops. The impact of the scenarios on four measures of alcohol-related harm were considered: total acute harms, alcohol-related violence, emergency department (ED) presentations and hospitalizations.

    RESULTS: Simulation of a 3 a.m. (rather than 5 a.m.) closing time resulted in an estimated 12.3 ± 2.4% reduction in total acute alcohol-related harms, a 7.9 ± 0.8% reduction in violence, an 11.9 ± 2.1% reduction in ED presentations and a 9.5 ± 1.8% reduction in hospitalizations. Further reductions were achieved simulating a 1 a.m. closing time, including a 17.5 ± 1.1% reduction in alcohol-related violence. Simulated extensions to bottle shop trading hours resulted in increases in rates of all four measures of harm, although most of the effects came from increasing operating hours from 10 p.m. to 11 p.m.

    CONCLUSIONS: An agent-based simulation model suggests that restricting trading hours of licensed venues reduces rates of alcohol-related harm and extending trading hours of bottle shops increases rates of alcohol-related harm. The model can estimate the effects of a range of policy options.

  • 232.
    Atti, Anna Rita
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Forlani, Claudia
    de Ronchi, Diana
    Palmer, Katie
    Casadio, Paola
    Dalmonte, Edoardo
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Cognitive Impairment after Age 60: clinical and Social Correlates in the "Faenza Project"2010In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 21, no 4, p. 1325-1334Article in journal (Refereed)
    Abstract [en]

    A total of 7,389 dementia-free elderly (60–102 years old) enrolled in the "Faenza Project" (Northern Italy) were clinically evaluated by nurses and physicians with the aim of detecting the independent and combined association of medical and social factors with cognitive status. Cognitive Impairment No Dementia (CIND) was defined for MMSE scores ⩽ 2 standard deviations than the age- and education-corrected mean score obtained by the non-demented persons of the Faenza cohort. Logistic Regression analysis was used to estimate Odds Ratios and 95% Confidence Intervals (OR, 95%CI) for CIND. The diagnostic procedure identified 402 (5.4%) CIND cases. Diabetes (OR, 95%CI=1.6, 1.2–2.2), stroke (OR, 95%CI=1.9, 1.4–2.6), and depressive symptoms (OR, 95%CI=1.9, 1.4–2.7) emerged as the most relevant medical comorbidities of CIND. Low education (OR, 95%CI=1.8, 1.1–2.9), low Socio Economic Status (SES) (OR, 95%CI=1.5, 1.1–2.1), and unmarried status (OR, 95%CI=1.7, 1.2–2.5) were associated with CIND. Medical and social factors were independently related to CIND occurrence. In comparison to subjects without any of the above mentioned conditions, subjects with one medical and one social factor had an OR, 95%CI for CIND equal to 6.0, 2.9–12.4. The strength of the association increased when more of those conditions occurred in combination, suggesting a synergistic effect. Despite some methodological limitations, data from this cross-sectional population-based Italian study show that low education, low SES, unmarried status together with diabetes, stroke, and depressive symptoms are related to cognitive impairment in the general population. The interaction of medical and social factors further increases the probability of CIND.

  • 233.
    Attoff, Kristina
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    In vitro developmental neurotoxicity of acrylamide2016Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    The number of children with neurodevelopmental disorders is increasing worldwide which makes it a public concern. Exposure to environmental chemicals has been reported as a source of developmental neurotoxicity. There is also an increase in the number of chemicals reaching the global market each year and currently there are thousands of substances that have not yet been tested for developmental neurotoxicity. The current developmental neurotoxicity testing guidelines are time consuming, expensive, require a lot of animals and have relatively low sensitivity understanding for the mechanisms of toxicology. The field of developmental neurotoxicity testing is in need of a paradigm shift to the use of alternative in vitro methods capable of testing and screening large number of substances. The next generation developmental neurotoxicity testing will consist of both in silico and in vitro testing that has to be used in a combined fashion so that it will generate a more rapid and efficient toxicity testing. The methods need to be standardized between laboratories so that reproducible data can be obtained. Simple endpoints will simply not be enough for in vitro developmental neurotoxicity testing models. Rather, a battery of more refined endpoints that pinpoints the specific toxicity of a compound, discriminate between different neural subpopulations and different stages of neural differentiation is crucial for success. The use of mRNA biomarkers could be a good example of such an endpoint, and have been suggested to be valuable in detecting developmental neurotoxicity. This thesis will give a broad overview of different alternative in vitro models for developmental neurotoxicity. Developmental neurotoxicity of acrylamide was investigated by using selected cell models and endpoints. Acrylamide is a well-known neurotoxic compound and most people get exposed to the compound by food consumption and from environmental pollutants. Since acrylamide crosses the placenta barrier, the fetus is also being exposed and the risk for adverse effects in the developing nervous system is overwhelming. The neural progenitor cell line C17.2 and the neuroblastoma cell line SH-SY5Y were used to study proliferation and differentiation as indicators for developmental neurotoxicity. The reduced neurite outgrowth in the SH-SY5Y cell model occurred at up to seven orders of magnitude lower than what have been previously shown for different neural cell systems. Acrylamide also affected the differentiation process in both neurons and glia cells in the C17.2 cell line. We show that acrylamide attenuated neural differentiation at seven orders of magnitude lower concentrations than the estimated plasma concentration of free acrylamide in the fetus. The fact that low concentrations seem to delay the differentiation process in both cell lines, raises cause for an alarm for developmental neurotoxicity induced by acrylamide.  

  • 234.
    Attoff, Kristina
    et al.
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Kertika, Dimitra
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Lundqvist, Jessica
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Oredsson, S.
    Forsby, Anna
    Stockholm University, Faculty of Science, Department of Neurochemistry. Stockholm Univ, Dept Neurochem, S-10691 Stockholm, Sweden.
    Acrylamide affects proliferation and differentiation of the neural progenitor cell line C17.2 and the neuroblastoma cell line SH-SY5Y2016In: Toxicology in Vitro, ISSN 0887-2333, E-ISSN 1879-3177, Vol. 35, p. 100-111Article in journal (Refereed)
    Abstract [en]

    Acrylamide is a well-known neurotoxic compound and people get exposed to the compound by food consumption and environmental pollutants. Since acrylamide crosses the placenta barrier, the fetus is also being exposed resulting in a risk for developmental neurotoxicity. In this study, the neural progenitor cell line C17.2 and the neuroblastoma cell line SH-SY5Y were used to study proliferation and differentiation as alerting indicators for developmental neurotoxicity. For both cell lines, acrylamide reduced the number of viable cells by reducing proliferation and inducing cell death in undifferentiated cells. Acrylamide concentrations starting at 10 fM attenuated the differentiation process in SH-SY5Y cells by sustaining cell proliferation and neurite outgrowth was reduced at concentrations from 10 pM. Acrylamide significantly reduced the number of neurons starting at 1 mu M and altered the ratio between the different phenotypes in differentiating C17.2 cell cultures. Ten micromolar of acrylamide also reduced the expression of the neuronal and astrocyte biomarkers. Although the neurotoxic concentrations in the femtomolar range seem to be specific for the SH-SY5Y cell line, the fact that micromolar concentrations of acrylamide seem to attenuate the differentiation process in both cell lines raises the interest to further investigations on the possible developmental neurotoxicity of acrylamide.

  • 235. Atzendorf, Josefine
    et al.
    Apfelbacher, Christian
    Gomes de Matos, Elena
    Kraus, Ludwig
    Stockholm University, Faculty of Social Sciences, Department of Public Health Sciences. IFT Institut für Therapieforschung, Germany; Eötvös-Loránd-Universität, Hungary.
    Piontek, Daniela
    Patterns of multiple lifestyle risk factors and their link to mental health in the German adult population: a cross-sectional study2018In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 8, no 12, article id e022184Article in journal (Refereed)
    Abstract [en]

    Objectives Lifestyle risk factors, such as drinking or unhealthy diet, can expotentiate detrimental health effects. Therefore, it is important to investigate multiple lifestyle risk factors instead of single ones. The study aims at: (1) identifying patterns of lifestyle risk factors within the adult general population in Germany and (2) examining associations between the extracted patterns and external factors.

    Design Cross-sectional study.

    Setting General German adult population (aged 18–64 years).

    Participants Participants of the 2015 Epidemiological Survey of Substance Abuse (n=9204).

    Primary outcome measures Lifestyle risk factors (daily smoking, at-risk alcohol consumption, unhealthy diet, low physical activity, weekly use of pharmaceuticals, as well as consumption of cannabis and other illicit drugs).

    Results A latent class analysis was applied to identify patterns of lifestyle risk factors, and a multinomial logistic regression was carried out to examine associations between the extracted classes and external factors. A total of four classes were extracted which can be described as healthy lifestyle (58.5%), drinking lifestyle (24.4%), smoking lifestyle (15.4%) and a cumulate risk factors lifestyle (1.7%). Individuals who were male, at younger age and single as well as individuals with various mental health problems were more likely to show multiple lifestyle risk factors.

    Conclusions Healthcare professionals should be aware of correlations between different lifestyle risk factors as well as between lifestyle risk groups and mental health. Health promotion strategies should further focus especially on younger and single men.

    This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

  • 236. Atzendorf, Josefine
    et al.
    Aschenbrenner, Annika Berit
    de Matos, Elena Gomes
    Kraus, Ludwig
    Stockholm University, Faculty of Social Sciences, Department of Public Health Sciences. FT Institut für Therapieforschung, Germany; Eötvös Loránd University, Hungary.
    Kroeger, Christoph
    Delle, Simone
    Piontek, Daniela
    E-Zigaretten: Einschätzung vonGesundheitsgefahren undNutzung zur Tabakentwöhnung2018In: Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz, ISSN 1436-9990, Vol. 61, no 11, p. 1415-1421Article in journal (Refereed)
    Abstract [de]

    BackgroundThe perception that e-cigarettes are less harmful than traditional tobacco products can influence the consumption of e-cigarettes.ObjectivesThree questions were examined: (1)How do different population groups perceive health risks of e-cigarettes? (2)Do sociodemographic variables explain differences in the risk assessment of e-cigarettes? (3)Does the perception of health risks predict the use of e-cigarettes for smoking cessation?MethodsData came from the 2015 Epidemiological Survey of Substance Abuse (ESA) with asample size of n=9204 participants, aged 18 to 64years (response rate 52.2%). Data were collected by telephone, online, or by written questionnaires. Assessments of risk perception of e-cigarettes and conventional cigarettes (more harmful, just as harmful, less harmful, do not know) were compared. Descriptive statistics and logistic regressions were performed.ResultsIndividuals with lower education rated e-cigarettes as more harmful. Older people and women perceived e-cigarettes as just as harmful. Smokers considered e-cigarettes to be more harmful than or just as harmful as conventional tobacco products. The likelihood of using e-cigarettes for smoking cessation was higher if people thought they were less harmful than conventional cigarettes.ConclusionsOnly one-third of the population knows that e-cigarettes are less harmful to health than conventional cigarettes. The perception of health risks is related to the usage of e-cigarettes for smoking cessation.

  • 237. Atzendorf, Josefine
    et al.
    Gomes de Matos, Elena
    Kröger, Christoph
    Kraus, Ludwig
    Stockholm University, Faculty of Social Sciences, Department of Public Health Sciences. IFT Institut für Therapieforschung, Germany; Eötvös-Loránd-Universität, Hungary.
    Piontek, Daniela
    Die Nutzung von E-Zigaretten in der deutschen Bevölkerung – Ergebnisse des Epidemiologischen Suchtsurvey 20152019In: Das Gesundheitswesen, ISSN 0941-3790, E-ISSN 1439-4421, Vol. 81, no 02, p. 137-143Article in journal (Refereed)
    Abstract [en]

    Aim Estimates of e-cigarette consumption in Germany vary considerably. The use of e-cigarettes for tobacco cessation is critically discussed. Based on current data, the distribution of the consumption of e-cigarettes and their use in the adult general population of Germany will be presented.

    Methods The 2015 Epidemiological Survey of Substance Abuse, a nationwide survey of 18 to 64 year-old people in Germany (n=9,204, response rate: 52,2%), was used as data basis.

    Results E-cigarettes were known to most of the respondents (85,3%, 43,5 Mio.), whereas only 2,9% (1,5 Mio.) used e-cigarettes in the last 30 days. Higher risk of consuming e-cigarettes was seen in younger people (OR=0,95, 95%-KI=(0,93; 0,97)), men (OR=1,45, 95%-KI=(1,02; 2,07)) and smokers (OR=12,53, 95%-KI=(8,71; 18,03)). About a third of smokers and ex-smokers of conventional cigarettes (36,6%) who consumed e-cigarettes used these for tobacco cessation of which one fifth (21,3%) was able to quit smoking.

    Conclusion E-cigarette users seem to be more likely to be male, younger and smokers of conventional cigarettes. In addition to curiosity, the change in smoking behavior is an important motive for consumption. The results indicate that the use of e-cigarettes can contribute to tobacco cessation, the majority of users, however, continue to consume conventional and/or e-cigarettes.

  • 238. Aufschnaiter, Andreas
    et al.
    Habernig, Lukas
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. University of Graz, Austria.
    Kohler, Verena
    Diessl, Jutta
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Carmona-Gutierrez, Didac
    Eisenberg, Tobias
    Keller, Walter
    Büttner, Sabrina
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. University of Graz, Austria.
    The Coordinated Action of Calcineurin and Cathepsin D Protects Against alpha-Synuclein Toxicity2017In: Frontiers in Molecular Neuroscience, ISSN 1662-5099, Vol. 10, article id 207Article in journal (Refereed)
    Abstract [en]

    The degeneration of dopaminergic neurons during Parkinson's disease (PD) is intimately linked to malfunction of alpha-synuclein (alpha Syn), the main component of the proteinaceous intracellular inclusions characteristic for this pathology. The cytotoxicity of alpha Syn has been attributed to disturbances in several biological processes conserved from yeast to humans, including Ca2+ homeostasis, general lysosomal function and autophagy. However, the precise sequence of events that eventually results in cell death remains unclear. Here, we establish a connection between the major lysosomal protease cathepsin D (CatD) and the Ca2+/calmodulin-dependent phosphatase calcineurin. In a yeast model for PD, high levels of human alpha Syn triggered cytosolic acidification and reduced vacuolar hydrolytic capacity, finally leading to cell death. This could be counteracted by overexpression of yeast CatD (Pep4), which re-installed pH homeostasis and vacuolar proteolytic function, decreased alpha Syn oligomers and aggregates, and provided cytoprotection. Interestingly, these beneficial effects of Pep4 were independent of autophagy. Instead, they required functional calcineurin signaling, since deletion of calcineurin strongly reduced both the proteolytic activity of endogenous Pep4 and the cytoprotective capacity of overexpressed Pep4. Calcineurin contributed to proper endosomal targeting of Pep4 to the vacuole and the recycling of the Pep4 sorting receptor Pep1 from prevacuolar compartments back to the trans-Golgi network. Altogether, we demonstrate that stimulation of this novel calcineurin-Pep4 axis reduces alpha Syn cytotoxicity.

  • 239. Aufschnaiter, Andreas
    et al.
    Kohler, Verena
    Büttner, Sabrina
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. University of Graz, Austria.
    Taking out the garbage: cathepsin D and calcineurin in neurodegeneration2017In: Neural Regeneration Research, ISSN 1673-5374, E-ISSN 1876-7958, Vol. 12, no 11, p. 1776-1779Article, review/survey (Refereed)
    Abstract [en]

    Cellular homeostasis requires a tightly controlled balance between protein synthesis, folding and degradation. Especially long-lived, post-mitotic cells such as neurons depend on an efficient proteostasis system to maintain cellular health over decades. Thus, a functional decline of processes contributing to protein degradation such as autophagy and general lysosomal proteolytic capacity is connected to several age-associated neurodegenerative disorders, including Parkinson's, Alzheimer's and Huntington's diseases. These so called proteinopathies are characterized by the accumulation and misfolding of distinct proteins, subsequently driving cellular demise. We recently linked efficient lysosomal protein breakdown via the protease cathepsin D to the Ca2+/calmodulin-dependent phosphatase calcineurin. In a yeast model for Parkinson's disease, functional calcineurin was required for proper trafficking of cathepsin D to the lysosome and for recycling of its endosomal sorting receptor to allow further rounds of shuttling. Here, we discuss these findings in relation to present knowledge about the involvement of cathepsin D in proteinopathies in general and a possible connection between this protease, calcineurin signalling and endosomal sorting in particular. As dysregulation of Ca2+ homeostasis as well as lysosomal impairment is connected to a plethora of neurodegenerative disorders, this novel interplay might very well impact pathologies beyond Parkinson's disease.

  • 240. Aufschnaiter, Andreas
    et al.
    Kohler, Verena
    Walter, Corvin
    Tosal-Castano, Sergi
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Habernig, Lukas
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Wolinski, Heimo
    Keller, Walter
    Vögtle, F-Nora
    Büttner, Sabrina
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. University of Graz, Austria.
    The Enzymatic Core of the Parkinson's Disease-Associated Protein LRRK2 Impairs Mitochondria Biogenesis in Aging Yeast2018In: Frontiers in Molecular Neuroscience, ISSN 1662-5099, Vol. 11, article id 205Article in journal (Refereed)
    Abstract [en]

    Mitochondrial dysfunction is a prominent trait of cellular decline during aging and intimately linked to neuronal degeneration during Parkinson's disease (PD). Various proteins associated with PD have been shown to differentially impact mitochondrial dynamics, quality control and function, including the leucine-rich repeat kinase 2 (LRRK2). Here, we demonstrate that high levels of the enzymatic core of human LRRK2, harboring GTPase as well as kinase activity, decreases mitochondrial mass via an impairment of mitochondria! biogenesis in aging yeast. We link mitochondrial depletion to a global downregulation of mitochondria-related gene transcripts and show that this catalytic core of LRRK2 localizes to mitochondria and selectively compromises respiratory chain complex IV formation. With progressing cellular age, this culminates in dissipation of mitochondrial transmembrane potential, decreased respiratory capacity, ATP depletion and generation of reactive oxygen species. Ultimately, the collapse of the mitochondrial network results in cell death. A point mutation in LRRK2 that increases the intrinsic GTPase activity diminishes mitochondrial impairment and consequently provides cytoprotection. In sum, we report that a downregulation of mitochondrial biogenesis rather than excessive degradation of mitochondria underlies the reduction of mitochondrial abundance induced by the enzymatic core of LRRK2 in aging yeast cells. Thus, our data provide a novel perspective for deciphering the causative mechanisms of LRRK2-associated PD pathology.

  • 241. Auguer, Nathalie
    et al.
    Le Serbon, Emelie
    Rostila, Mikael
    Stockholm University, Faculty of Social Sciences, Department of Sociology.
    Leaving Sweden behind: gains in life expectancy in Canada2015In: Scandinavian Journal of Public Health, ISSN 1403-4948, E-ISSN 1651-1905, Vol. 43, no 4, p. 340-347Article in journal (Refereed)
    Abstract [en]

    Aims: Sweden and Canada are known for quality of living and exceedingly high life expectancy, but recent data on how these countries compare are lacking. We measured life expectancy in Canada and Sweden during the past decade, and identified factors responsible for changes over time. Methods: We calculated life expectancy at birth for Canada and Sweden annually from 2000 to 2010, and determined the ages and causes of death responsible for the gap between the two countries using Arriaga's method. We determined how population growth, ageing, and mortality influenced the number of deaths over time. Results: During 2000-2010, life expectancy in Canada caught up with Sweden for men, and surpassed Sweden by 0.4 years for women. Sweden lost ground owing to a slower reduction in circulatory and tumour mortality after age 65 years compared with Canada. Nonetheless, population ageing increased the number of deaths in Canada, especially for mental and nervous system disorders. In Sweden, the number of deaths decreased. Conclusions: In only one decade, life expectancy in Canada caught up and surpassed Sweden due to rapid improvements in circulatory and tumour mortality. Population ageing increased the number of deaths in Canada, potentially stressing the health care system more than in Sweden.

  • 242. Augustsson, Hanna
    et al.
    von Thiele Schwarz, Ulrica
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Karolinska Institutet, Sweden.
    Stenfors-Hayes, Terese
    Hasson, Henna
    Investigating Variations in Implementation Fidelity of an Organizational-Level Occupational Health Intervention2015In: International Journal of Behavioral Medicine, ISSN 1070-5503, E-ISSN 1532-7558, Vol. 22, no 3, p. 345-355Article in journal (Refereed)
    Abstract [en]

    The workplace has been suggested as an important arena for health promotion, but little is known about how the organizational setting influences the implementation of interventions. The aims of this study are to evaluate implementation fidelity in an organizational-level occupational health intervention and to investigate possible explanations for variations in fidelity between intervention units. The intervention consisted of an integration of health promotion, occupational health and safety, and a system for continuous improvements (Kaizen) and was conducted in a quasi-experimental design at a Swedish hospital. Implementation fidelity was evaluated with the Conceptual Framework for Implementation Fidelity and implementation factors used to investigate variations in fidelity with the Framework for Evaluating Organizational-level Interventions. A multi-method approach including interviews, Kaizen notes, and questionnaires was applied. Implementation fidelity differed between units even though the intervention was introduced and supported in the same way. Important differences in all elements proposed in the model for evaluating organizational-level interventions, i.e., context, intervention, and mental models, were found to explain the differences in fidelity. Implementation strategies may need to be adapted depending on the local context. Implementation fidelity, as well as pre-intervention implementation elements, is likely to affect the implementation success and needs to be assessed in intervention research. The high variation in fidelity across the units indicates the need for adjustments to the type of designs used to assess the effects of interventions. Thus, rather than using designs that aim to control variation, it may be necessary to use those that aim at exploring and explaining variation, such as adapted study designs.

  • 243.
    Aust, Christina
    et al.
    Stockholm University, Faculty of Social Sciences, Specialpedagogiska institutionen.
    Tallkvist, Anna
    Stockholm University, Faculty of Social Sciences, Specialpedagogiska institutionen.
    Idrott för barn och ungdomar med funktionsnedsättning2008Student thesis
  • 244.
    Awah, Nancy
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Studies on Plasmodium falciparum asexual blood stage antigens: RAP-2/RSP-2 and Pf332 in focus2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The life cycle of the malaria parasite is very complex and provides a number of potential targets for vaccination. In this thesis, data on two plasmodial asexual blood stage antigens (RAP-2 and Pf332) are presented.

    A partial aim of the work presented herein was to investigate the mechanisms responsible for the destruction of erythroid cells in anaemia, and more specifically to define the role of the rhoptry associated protein (RAP)-2 and other members of the RAP complex, RAP-1 and -3 in processes resulting in anaemia. Antibodies to the RAP complex were shown to have the potential to mediate the destruction of RAP-2-tagged erythroid cells by phagocytosis or by complement activation and lysis. In addition, antibodies to RAP-1 and RAP-2 could induce the apoptotic death of RAP-2- tagged erythroblasts. The frequency and functionality of naturally occurring RAP-2 antibodies in the sera of anaemic and non-anaemic Cameroonian children were also investigated. All sera tested contained RAP-2-reactive antibodies by both immunofluorescence and flow cytometry. The anaemic group of children had higher levels of IgG than the non-anaemic ones, while the levels of IgM were similar. With respect to IgG subclasses, higher levels of IgG3 were seen in the non-anaemic individuals as compared to anaemic subjects. The non-anaemic individuals recognised a greater proportion of RAP-2-tagged RBCs and activated complement to a greater extent than the anaemic ones.

    Earlier studies observed that humans continuously exposed to malaria, recognised Pf332 extensively. Further studies revealed that Pf332 antibodies were able to inhibit parasite growth and cytoadherence in vitro. Making use of Pf332-C231, a sub-fragment of Pf332, we studied the effects/mode of action of C231-specific antibodies on P. falciparum parasite growth and development in vitro. The antibodies appeared to act mainly on late stage parasites by two main mechanisms: 1) through the induction of abnormal/pyknotic parasites, and, 2) RBC lysis (disintegration of RBCs), thus limiting parasite growth and development. The antibody isotype in this context was IgG. Following the removal of immune pressure, parasites resumed growth, albeit at a much slower rate. The results suggest that during natural infections, antibodies to C231 could play a role in parasite control.

    In summary, these data suggest that antibodies to both antigens could be instrumental in immune responses leading to disease control, but could also mediate pathology.

  • 245.
    Awah, Nancy
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Balogun, Halima
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Achidi, E.
    Mariuba, L. A.
    Nogueira, P. A.
    Orlandi, P.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Gysin, J.
    Berzins, Klavs
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Antibodies to the Plasmodium falciparum rhoptry protein RAP-2/RSP-2 in relation to anaemia in Cameroonian children2011In: Parasite immunology (Print), ISSN 0141-9838, E-ISSN 1365-3024, Vol. 33, no 2, p. 104-115Article in journal (Refereed)
    Abstract [en]

    Previous studies have implicated reactive antibodies to the low molecular weight rhoptry-associated proteins (RAP-1, RAP-2/RSP-2 and RAP-3) in erythroid cell destruction during Plasmodium falciparum infection. In this pilot study, the frequency, specificity and functional capacity of naturally acquired anti-RAP-2/RSP-2 antibodies were investigated in the sera of anaemic and nonanaemic malaria-infected Cameroonian children. All sera recognized RAP-2/RSP-2 by FACS, irrespective of the clinical status of the subjects. However, the anaemic children showed higher levels of IgG antibodies than the nonanaemic group, while both groups showed similar levels of IgM antibodies. Only few individuals had detectable levels of RAP-2/RSP-2-specific IgG1 and IgG3 subclass antibodies, while no IgG2 and IgG4 subclass antibodies were detected in these subjects. By ELISA, the anaemic group tended to show higher levels of antibodies to RAP-2/RSP-2 regarding all antibody classes tested, except for IgG4 and IgE. Unexpectedly, sera from the nonanaemic group activated complement to a greater extent than those from the anaemic group. These results need to be confirmed in extended studies but indicate that the effector functions of the RAP-2/RSP-2-reactive antibodies may be more important than their amounts. Such antibodies could play a role in both immunity and pathogenesis during P. falciparum infection.

  • 246. Axelsson, J.
    et al.
    Kecklund, Göran
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Gustavsson, P.
    Rudman, A.
    Selection into shift and night work2013Conference paper (Refereed)
  • 247.
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Sleep, appearance and social interactions2014Conference paper (Other academic)
  • 248.
    Axelsson, John
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Kecklund, Göran
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Sömn och fysisk aktivitet2016In: FYSS 2017: fysisk aktivitet i sjukdomsprevention och sjukdomsbehandling, Stockholm: Läkartidningen förlag AB , 2016, 3, p. 171-183Chapter in book (Other academic)
  • 249. Axelsson, John
    et al.
    Kecklund, Göran
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Akerstedt, Torbjörn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Donofrio, Paolo
    Lekander, Mats
    Ingre, Michael
    Sleepiness and performance in response to repeated sleep restriction and subsequent recovery during semi-laboratory conditions.2008In: Chronobiol Int, ISSN 1525-6073, Vol. 25, no 2, p. 297-308Article in journal (Refereed)
    Abstract [en]

    Sleepiness and performance in response to repeated sleep restriction and subsequent recovery during semi-laboratory conditions.

    Axelsson J, Kecklund G, Akerstedt T, Donofrio P, Lekander M, Ingre M.

    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. john.axelsson@ki.se

    There is an ongoing debate of how best to measure the effects of sleep loss in a reliable and feasible way, partly because well controlled laboratory studies and field studies have come to different conclusions. The aims of the present study were to investigate both sleepiness and performance in response to long-term sleep restriction and recovery in a semi-laboratory environment, investigate order effects (i.e., whether levels return to baseline) in a study with seven days of recovery, and characterize individual differences in tolerance to restricted sleep. Nine healthy men (age 23-28 yrs) participated in the protocol, which included one habituation day (sleep 23:00-07:00 h), two baseline days (23:00-07:00 h), five days with restricted sleep (03:00-07:00 h), and seven recovery days (23:00-07:00 h). Participants went outdoors at least twice each day. Reaction-time tests were performed at 08:00, 14:00, and 20:00 h each day in the laboratory. Sleepiness was self-rated by the Karolinska Sleepiness Scale (KSS)after each test. The mixed-effect regression models showed that each day of restricted sleep resulted in an increase of sleepiness by 0.64+/- .05 KSS units (a nine-step scale, p < .001), increase of median reaction times of 6.6+/- 1.6 ms ( p = .003), and increase of lapses/test of 0.69 +/- .16 ms ( p < .001). Seven days of recovery allowed participants to return to the baseline for sleepiness and median reaction time, but not for lapses.The individual differences were larger for performance measures than for sleepiness; the between-subject standard deviation for the random intercept was in the magnitude of the effects of 1.1 days of restricted sleep for sleepiness, 6.6 days of restricted sleep for median reaction time, and 3.2 days for lapses. In conclusion, the present study shows that sleepiness is closely related to sleep pressure, while performance measures, to a larger extent, appear determined by specific individual traits. Moreover, it is suggested to measure sleepiness in a standardized situation so as to minimize the influences of contextual factors.

  • 250.
    Axelsson, John
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Kecklund, Göran
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Tigerström, L
    Does rapid eye movement (REM) sleep prepare the brain for wakening?2014In: Journal of sleep research, Special issue: 22nd Congress of the European Sleep Research Society, 16-20 September, 2014, Tallinn, Estonia, 2014Conference paper (Other academic)
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