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  • 3701.
    Winge, Monica
    et al.
    Karolinska Institute, Sweden.
    Wangler, Benkt
    University of Skövde, Sweden.
    Johansson, Lars-Åke
    Alkit Communications, Sweden.
    Nyström, Monica
    Karolinska Institute, Sweden.
    Lindh-Waterworth, Eva
    Umeå University, Sweden.
    CO-CARE - Collaborative Health and Social Care2008In: Proceedings of 13th International Symposium for Health Information Management Research / [ed] P. S. Bath, K. Day, T. Norris, Massey University, New Zealand , 2008, p. 113-124Conference paper (Refereed)
    Abstract [en]

    In this paper we discuss the fact that more and more patients are treated in their homes by a set of organizations, sometimes with different ownership. We explore how this poses new and stronger demands on health care and home service staff, as well as on different managerial and operational levels, to improve their communication and collaboration. We emphasize the need for managers in different organizations to agree on ways and forms of communication and collaboration between the operational levels, and the particular importance of this during procurement of home care services. As a result a number of methodological measures, strategies and IT solutions to support organizational development, coordination and collaboration are suggested.

  • 3702.
    Winther, Åsa M E
    et al.
    Stockholm University, Faculty of Science, Department of Zoology, Functional Morphology.
    Acebes, Angel
    Ferrús, Alberto
    Tachykinin-related peptides modulate odor perception and locomotoractivity in Drosophila2006In: Molecular and Cellular Neuroscience, ISSN 1044-7431, E-ISSN 1095-9327, Vol. 31, no 3, p. 399-406Article in journal (Refereed)
    Abstract [en]

    The invertebrate tachykinin-related peptides (TKRPs) constitute aconserved family, structurally related to the mammalian tachykinins,including members such as substance P and neurokinins A and B.Although their expression has been documented in the brains of insectsand mammals, their neural functions remain largely unknown,particularly in behavior. Here, we have studied the role of TKRPs inDrosophila. We have analyzed the olfactory perception and thelocomotor activity of individuals in which TKRPs are eliminated inthe nervous system specifically, by using RNAi constructs to silencegene expression. The perception of specific odorants and concentrationsis modified towards a loss of sensitivity, thus resulting in asignificant change of the behavioral response towards indifference. Inlocomotion assays, the TKRP-deficient flies show hyperactivity. Weconclude that these peptides are modulators of olfactory perceptionand locomotion activity in agreement with their abundant expression inthe olfactory lobes and central complex. In these brain centers, TKRPsseem to enhance the regulatory inhibition of the neurons in which theyare expressed.

  • 3703.
    Winther, Åsa M E
    et al.
    Stockholm University, Faculty of Science, Department of Zoology.
    Kashai, Lily
    Stockholm University, Faculty of Science, Department of Zoology.
    Martin, Jean-René
    Neuropeptides in the central complex modulate locomotor behavior2008Conference paper (Other academic)
  • 3704.
    Winther, Åsa M E
    et al.
    Stockholm University, Faculty of Science, Department of Zoology. funktionell morfologi.
    Nässel, Dick R
    Stockholm University, Faculty of Science, Department of Zoology. funktionell morfologi.
    Ignell, Rickard
    Peptidergic signaling in the antennal lobe modulates olfaction2007In: 20th European Drosophila Research Coference: EDRC 2007, 2007Conference paper (Other academic)
    Abstract [en]

    The dtk gene in Drosophila encodes five different neuropeptides designated Drosophila tachykinins (DTK 1-5) that are expressed in about 100 neurons in the brain. Two tachykinin receptors (DTKR and NKD) have been identified in Drosophila. Specific neurons of the antennal lobe (AL), the primary center for olfactory processing in the Drosophila brain, express DTKs and the receptor DTKR. The DTKs are colocalized with the inhibitory transmitter GABA in many of the local interneurons (LNs) of the AL. We have investigated the roles of DTKs and DTKR in olfactory behavior by interfering with DTK signaling. By employing the Gal4/UAS system we have directed overexpression or knock-down (using RNAi) of peptides or receptor to different neuron types of the AL. Olfactory behavior was tested in a trap-assay based on a choice of odorant or control. We tested flies with DTK deficiency in two different partly overlapping populations of LNs. We also tested flies that are virtually DTK null (driving the RNAi construct with the pan-neural elav-Gal4). DTK deficient flies were less attracted to some of the odors tested. To study the role of the DTKR we used Gal4 lines that drive expression in olfactory receptor neurons (ORNs), LNs and in projection neurons to overexpress (OE) or down-regulate the receptor. DTKR-OE in the ORNs resulted in flies more repelled (or less attracted) to some of the odors tested. DTKR-OE in a subpopulation of the LNs produced flies with the same behavioral phenotype. Flies with DTKR deficiency in the ORNs and LNs were more attracted to odors. Our results suggest that DTKs and DTKR are involved in the modulation of the response to odors at the levels of ORNs and LNs, possibly by modulating the inhibitory activity of GABA.

  • 3705. Winzer, Regina
    et al.
    Lindblad, Frank
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Uppsala University, Sweden.
    Sorjonen, Kimmo
    Lindberg, Lene
    Positive versus negative mental health in emerging adulthood: a national cross-sectional survey2014In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 14, p. 1238-Article in journal (Refereed)
    Abstract [en]

    Background: The dual continuum model suggests that positive mental health not only implies the absence of mental illness, but also constitutes an entity of its own. Measures that encompass both positive and negative mental health in young adults are rare. Thus, we assessed whether dimensions corresponding to positive and negative mental health could be identified in a sample of young individuals. Additionally, we explored how such dimensions were associated with potential health-related factors. Methods: We obtained data from the Swedish National Public Health Survey 2004-2009 (23,394 women, 18,274 men, aged 16-29 years). We used exploratory factor analysis (EFA) to identify relevant factors revealed by the 12-item General Health Questionnaire (GHQ-12) and confirmatory factor analysis (CFA) to verify the factor structure. We tested the significance of the difference between effects of potential health-related factors on positive mental health (PMH) and negative mental health (NMH). Results: The EFA for the GHQ-12 revealed a two factor model with negative items that had high positive loadings on one factor and lower negative loadings on the other factor. The positive items had loading trends that were opposite those of the negative items. The fit of this model was supported by the CFA, which yielded a significantly better match than a unidimensional model. When we investigated the associations between GHQ-scores and potential predictors of health, we found that most potential predictors had significant and opposing effects on both PMH and NMH; with the strongest effects from suicidal ideation and perceived humiliation. Conclusions: Our results could be seen to indicate that positive and negative mental health are distinct and complementary constructs. Still, the results of our factor analysis may specifically reflect the wording of the items. We conclude that the GHQ-12 is an appropriate tool for its original purpose, to detect psychiatric morbidity. More refined measures, including predictors of health, are needed to assess PMH and validate the bidimensionality hypothesis.

  • 3706. Wittchen, H.U.
    et al.
    Jacobi, F.
    Rehm, J.
    Gustavsson, A.
    Svensson, M.
    Jönsson, B.
    Olesen, J.
    Allgulander, C.
    Alonso, J.
    Faravelli, C.
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Jennum, P.
    Lieb, R.
    Maercker, A.
    van Os, J.
    Preisig, M.
    Salvador-Carulla, L.
    Simon, R.
    Steinhausen, H.-C.
    The size and burden of mental disorders and other disorders of the brain in Europe 20102011In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 21, no 9, p. 655-679Article in journal (Refereed)
    Abstract [en]

    Aims

    To provide 12-month prevalence and disability burden estimates of a broad range of mental and neurological disorders in the European Union (EU) and to compare these findings to previous estimates. Referring to our previous 2005 review, improved up-to-date data for the enlarged EU on a broader range of disorders than previously covered are needed for basic, clinical and public health research and policy decisions and to inform about the estimated number of persons affected in the EU.

    Method

    Stepwise multi-method approach, consisting of systematic literature reviews, reanalyses of existing data sets, national surveys and expert consultations. Studies and data from all member states of the European Union (EU-27) plus Switzerland, Iceland and Norway were included. Supplementary information about neurological disorders is provided, although methodological constraints prohibited the derivation of overall prevalence estimates for mental and neurological disorders. Disease burden was measured by disability adjusted life years (DALY).

    Results

    Prevalence: It is estimated that each year 38.2% of the EU population suffers from a mental disorder. Adjusted for age and comorbidity, this corresponds to 164.8 million persons affected. Compared to 2005 (27.4%) this higher estimate is entirely due to the inclusion of 14 new disorders also covering childhood/adolescence as well as the elderly. The estimated higher number of persons affected (2011: 165 m vs. 2005: 82 m) is due to coverage of childhood and old age populations, new disorders and of new EU membership states. The most frequent disorders are anxiety disorders (14.0%), insomnia (7.0%), major depression (6.9%), somatoform (6.3%), alcohol and drug dependence (> 4%), ADHD (5%) in the young, and dementia (1–30%, depending on age). Except for substance use disorders and mental retardation, there were no substantial cultural or country variations. Although many sources, including national health insurance programs, reveal increases in sick leave, early retirement and treatment rates due to mental disorders, rates in the community have not increased with a few exceptions (i.e. dementia). There were also no consistent indications of improvements with regard to low treatment rates, delayed treatment provision and grossly inadequate treatment.

    Disability: Disorders of the brain and mental disorders in particular, contribute 26.6% of the total all cause burden, thus a greater proportion as compared to other regions of the world. The rank order of the most disabling diseases differs markedly by gender and age group; overall, the four most disabling single conditions were: depression, dementias, alcohol use disorders and stroke.

    Conclusion

    In every year over a third of the total EU population suffers from mental disorders. The true size of “disorders of the brain” including neurological disorders is even considerably larger. Disorders of the brain are the largest contributor to the all cause morbidity burden as measured by DALY in the EU. No indications for increasing overall rates of mental disorders were found nor of improved care and treatment since 2005; less than one third of all cases receive any treatment, suggesting a considerable level of unmet needs. We conclude that the true size and burden of disorders of the brain in the EU was significantly underestimated in the past. Concerted priority action is needed at all levels, including substantially increased funding for basic, clinical and public health research in order to identify better strategies for improved prevention and treatment for disorders of the brain as the core health challenge of the 21st century.

  • 3707. Wohlfarth, Carolin
    et al.
    Schmitteckert, Stefanie
    Härtle, Janina D.
    Houghton, Lesley A.
    Dweep, Harsh
    Fortea, Marina
    Assadi, Ghazaleh
    Braun, Alexander
    Mederer, Tanja
    Pöhner, Sarina
    Becker, Philip P.
    Fischer, Christine
    Granzow, Martin
    Mönnikes, Hubert
    Mayer, Emeran A.
    Sayuk, Gregory
    Boeckxstaens, Guy
    Wouters, Mira M.
    Simrén, Magnus
    Lindberg, Greger
    Ohlsson, Bodil
    Schmidt, Peter Thelin
    Dlugosz, Aldona
    Agreus, Lars
    Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    D'Amato, Mauro
    Burwinkel, Barbara
    Bermejo, Justo Lorenzo
    Röth, Ralph
    Lasitschka, Felix
    Vicario, Maria
    Metzger, Marco
    Santos, Javier
    Rappold, Gudrun A.
    Martinez, Cristina
    Niesler, Beate
    miR-16 and miR-103 impact 5-HT4 receptor signalling and correlate with symptom profile in irritable bowel syndrome2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 14680Article in journal (Refereed)
    Abstract [en]

    Irritable bowel syndrome (IBS) is a gut-brain disorder involving alterations in intestinal sensitivity and motility. Serotonin 5-HT4 receptors are promising candidates in IBS pathophysiology since they regulate gut motor function and stool consistency, and targeted 5-HT4R selective drug intervention has been proven beneficial in subgroups of patients. We identified a single nucleotide polymorphism (SNP) (rs201253747) c.*61 T > C within the 5-HT4 receptor gene HTR4 to be predominantly present in diarrhoea-IBS patients (IBS-D). It affects a binding site for the miR-16 family and miR-103/miR-107 within the isoforms HTR4b/i and putatively impairs HTR4 expression. Subsequent miRNA-profiling revealed downregulation of miR-16 and miR-103 in the jejunum of IBS-D patients correlating with symptoms. In vitro assays confirmed expression regulation via three 3'UTR binding sites. The novel isoform HTR4b_2 lacking two of the three miRNA binding sites escapes miR-16/103/107 regulation in SNP carriers. We provide the first evidence that HTR4 expression is fine-tuned by miRNAs, and that this regulation is impaired either by the SNP c.*61 T > C or by diminished levels of miR-16 and miR-103 suggesting that HTR4 might be involved in the development of IBS-D.

  • 3708.
    Wojcik, Andrzej
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Jan Kochanowski University, Poland.
    Oestreicher, Ursula
    Barrios, Lleonard
    Vral, Anne
    Terzoudi, Georgia
    Ainsbury, Elizabeth
    Rothkamm, Kai
    Trompier, Francois
    Kulka, Ulrike
    The RENEB operational basis: complement of established biodosimetric assays2017In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 93, no 1, p. 15-19Article in journal (Refereed)
    Abstract [en]

    Purpose: To set up an operational basis of the Realizing the European Network of Biodosimetry (RENEB) network within which the application of seven established biodosimetric tools (the dicentric assay, the FISH assay, the micronucleus assay, the PCC assay, the gamma-H2AX assay, electron paramagnetic resonance and optically stimulated luminescence) will be compared and standardized among the participating laboratories. Methodology: Two intercomparisons were organized where blood samples and smartphone components were irradiated, coded and sent out to participating laboratories for dosimetric analysis. Moreover, an accident exercise was organized during which each RENEB partner had the chance to practice the procedure of activating the network and to handle large amounts of dosimetric results. Results: All activities were carried out as planned. Overall, the precision of dose estimates improved between intercomparisons 1 and 2, clearly showing the value of running such regular activities. Conclusions: The RENEB network is fully operational and ready to act in case of a major radiation emergency. Moreover, the high capacity for analyzing radiation-induced damage in cells and personal electronic devices makes the network suitable for large-scale analyses of low doses effects, where high numbers of samples must be scored in order to detect weak effects.

  • 3709.
    Wold Jakobsson, Joakim
    Stockholm University. Stockholm University, University Library. Stockholm University, Faculty of Social Sciences, Department of Special Education.
    Arbetssätt och individualisering för elever med diagnosen ADHD.: ”På medeltiden hade man säkert jättenytta av lite ADHD, som bra krigare och kung. Men det är inte de kriterier som gäller i dagens samhälle.”2010Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Attention Deficit Hyperactivity Disorder (ADHD) är en av skolans vanligaste diagnoser och det uppskattas att omkring 2-3 procent av den svenska skolans elever tillhör denna kategori. Syftet med denna studie har varit att undersöka vilka tolkningar som finns för begreppet ADHD. Det har även varit ett syfte att undersökt hur en kommun i Stockholms län, en grundskola i den valda kommunen och grundskolans idrottslärare arbetar utifrån styrdokumenten för att skapa en individualiserad undervisning för elever med diagnosen ADHD.

    Intervjuer har genomförts med en kommunanställd specialpedagog, rektorn på den valda grundskolan samt tre av grundskolans idrottslärare för att spegla arbetet i den dagliga verksamheten.

    Det studien har kommit fram till är att begreppet ADHD är ett väldigt komplicerat begrepp som skolan, kommunen och forskare har svårt att enas om gemensamma förklaringar till. Enligt grundskolans styrdokument är diagnoser inte nödvändiga, men de kan ses som en stor hjälp för skolan och skolans lärare när det kommer till deras förståelse för elevens beteende. Diagnosen ADHD kan ses som ett fenomen i sig för att ge förståelse för personer runt omkring eleven. Om diagnosen ADHD skall användas i skolan bör den endast användas för att hjälpa eleven att på bästa sätt utvecklas kunskapsmässigt och personligt.

    En slutsats är att det behövs mer utbildning om begreppet ADHD i skolan för att undervisningen skall individanpassas till eleven med diagnosen ADHD på bästa möjliga sätt. Intervjupersonerna i studien har samtliga ansett att de själva skulle behöva mer utbildning för att öka förståelsen för en av skolans vanligaste diagnoser, ADHD.

  • 3710. Wright, Alison E.
    et al.
    Darolti, Iulia
    Bloch, Natasha I.
    Oostra, Vicencio
    Sandkam, Ben
    Buechel, Severine D.
    Stockholm University, Faculty of Science, Department of Zoology.
    Kolm, Niclas
    Stockholm University, Faculty of Science, Department of Zoology.
    Breden, Felix
    Vicoso, Beatriz
    Mank, Judith E.
    Convergent recombination suppression suggests role of sexual selection in guppy sex chromosome formation2017In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 8, article id 14251Article in journal (Refereed)
    Abstract [en]

    Sex chromosomes evolve once recombination is halted between a homologous pair of chromosomes. The dominant model of sex chromosome evolution posits that recombination is suppressed between emerging X and Y chromosomes in order to resolve sexual conflict. Here we test this model using whole genome and transcriptome resequencing data in the guppy, a model for sexual selection with many Y-linked colour traits. We show that although the nascent Y chromosome encompasses nearly half of the linkage group, there has been no perceptible degradation of Y chromosome gene content or activity. Using replicate wild populations with differing levels of sexually antagonistic selection for colour, we also show that sexual selection leads to greater expansion of the non-recombining region and increased Y chromosome divergence. These results provide empirical support for longstanding models of sex chromosome catalysis, and suggest an important role for sexual selection and sexual conflict in genome evolution.

  • 3711. Wu, Yu-Tzu
    et al.
    Beiser, Alexa S.
    Breteler, Monique M. B.
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Helmer, Catherine
    Hendrie, Hugh C.
    Honda, Hiroyuki
    Ikram, M. Arfan
    Langa, Kenneth M.
    Lobo, Antonio
    Matthews, Fiona E.
    Ohara, Tomoyuki
    Peres, Karine
    Qiu, Chengxuan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Seshadri, Sudha
    Sjölund, Britt-Marie
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Skoog, Ingmar
    Brayne, Carol
    The changing prevalence and incidence of dementia over time - current evidence2017In: Nature Reviews Neurology, ISSN 1759-4758, E-ISSN 1759-4766, Vol. 13, no 6, p. 327-U79Article, review/survey (Refereed)
    Abstract [en]

    Dementia is an increasing focus for policymakers, civil organizations and multidisciplinary researchers. The most recent descriptive epidemiological research into dementia is enabling investigation into how the prevalence and incidence are changing over time. To establish clear trends, such comparisons need to be founded on population-based studies that use similar diagnostic and research methods consistently over time. This narrative Review synthesizes the findings from 14 studies that investigated trends in dementia prevalence (nine studies) and incidence (five studies) from Sweden, Spain, the UK, the Netherlands, France, the USA, Japan and Nigeria. Besides the Japanese study, these studies indicate stable or declining prevalence and incidence of dementia, and some provide evidence of sex-specific changes. No single risk or protective factor has been identified that fully explains the observed trends, but major societal changes and improvements in living conditions, education and healthcare might have favourably influenced physical, mental and cognitive health throughout an individual's life course, and could be responsible for a reduced risk of dementia in later life. Analytical epidemiological approaches combined with translational neuroscientific research could provide a unique opportunity to explore the neuropathology that underlies changing occurrence of dementia in the general population.

  • 3712. Wu, Yu-Tzu
    et al.
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Matthews, Fiona E.
    Lobo, Antonio
    Breteler, Monique M. B.
    Skoog, Ingmar
    Brayne, Carol
    Dementia in western Europe: epidemiological evidence and implications for policy making2016In: Lancet Neurology, ISSN 1474-4422, E-ISSN 1474-4465, Vol. 15, no 1, p. 116-124Article in journal (Refereed)
    Abstract [en]

    Dementia is receiving increasing attention from governments and politicians. Epidemiological research based on western European populations done 20 years ago provided key initial evidence for dementia policy making, but these estimates are now out of date because of changes in life expectancy, living conditions, and health profiles. To assess whether dementia occurrence has changed during the past 20-30 years, investigators of five different studies done in western Europe (Sweden [Stockholm and Gothenburg], the Netherlands [Rotterdam], the UK [England], and Spain [Zaragoza]) have compared dementia occurrence using consistent research methods between two timepoints in well-defined geographical areas. Findings from four of the five studies showed non-significant changes in overall dementia occurrence. The only significant reduction in overall prevalence was found in the study done in the UK, powered and designed explicitly from its outset to detect change across generations (decrease in prevalence of 22%; p=0.003). Findings from the study done in Zaragoza (Spain) showed a significant reduction in dementia prevalence in men (43%; p=0.0002). The studies estimating incidence done in Stockholm and Rotterdam reported non-significant reductions. Such reductions could be the outcomes from earlier population-level investments such as improved education and living conditions, and better prevention and treatment of vascular and chronic conditions. This evidence suggests that attention to optimum health early in life might benefit cognitive health late in life. Policy planning and future research should be balanced across primary (policies reducing risk and increasing cognitive reserve), secondary (early detection and screening), and tertiary (once dementia is present) prevention. Each has their place, but upstream primary prevention has the largest effect on reduction of later dementia occurrence and disability.

  • 3713.
    Wulff, Cornelia
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Lindfors, Petra
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Sverke, Magnus
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Childhood General Mental Ability and Midlife Psychosocial Work Characteristics as Related to Mental Distress, Neck/Shoulder Pain and Self-rated Health in Working Women and Men2011In: Journal of Occupational Health, ISSN 1341-9145, E-ISSN 1348-9585, Vol. 53, no 6, p. 439-446Article in journal (Refereed)
    Abstract [en]

    Childhood General Mental Ability and Midlife Psychosocial Work Characteristics as Related to Mental Distress, Neck/Shoulder Pain and Self-rated Health in Working Women and Men: Cornelia WULFF, et al. Department of Psychology, Stockholm University, Sweden Psychosocial work characteristics including high demands, lack of control and poor social support have consistently been linked to poor health as has poor general mental ability (GMA). However, less is known about the relationships between stable individual factors such as GMA, psychosocial work characteristics and health. Objective: The present study investigated how childhood mental ability and psychosocial work characteristics relate to health in terms of mental distress, neck/shoulder pain (NSP) and self-rated health (SRH). Methods: Data on childhood GMA, occupational level, self-reports of demands, control and social support and health (mental distress, NSP and SRH) in midlife came from working women (n=271) and men (n=291) included in a Swedish school cohort. Hierarchical regression analyses, controlling for occupational level, were used to examine associations between childhood GMA, self-reports of high demands, low control and poor social support and the three health indicators. Taking into consideration the gendered labor market and variations in health patterns between women and men, gender specific analyses were performed. Results: There were no significant associations between childhood GMA and health indicators. Further, there were no significant interactions between GMA and psychosocial work factors. As regards the strength of the associations between GMA, psychosocial work factors and health, no consistent differences emerged between women and men. Conclusions: In a cohort of healthy and working middle-aged women and men, self-reports of current psychosocial work characteristics seem to be more strongly linked to health, than are stable childhood factors such as GMA.

  • 3714.
    Wulff, Cornelia
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Lindfors, Petra
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Sverke, Magnus
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Do general mental ability and psychosocial work characteristics predict different aspects of health in middle-aged working women and men?Manuscript (preprint) (Other academic)
    Abstract [en]

    Psychosocial work conditions including high demands, lack of control and poor support have been linked to poor health. Yet, it is unclear whether individual factors such as general mental ability (GMA) are important. Objective: The present study set out to investigate how childhood mental ability and psychosocial work characteristics relate to positive and negative health indicators. Methods: Data on childhood GMA, occupational level, self-reports of demands, control and social support and negative health indicators (anxiety and musculoskeletal disorders) and positive health indicators (sense of coherence and self-rated health) in midlife came from a cohort of working women (n=271) and men (n=291). Hierarchical regression analyses, with and without controlling for occupational level, were used to examine associations between childhood GMA and self-reports of high demands, low control and poor social support and the four health indicators. Taking into consideration the gendered labor market and variations in health patterns between women and men, gender specific analyses were performed. Results: The analyses showed no associations between childhood GMA and the health indicators. Further, there were no significant interactions between GMA and the psychosocial work factors. Moreover, the overall impact of occupational level was low and controlling for occupational level did not change the overall findings. Conclusions: In a fairly homogeneous cohort of healthy and working middle-aged women and men, current psychosocial work conditions are more strongly linked to self-reports of health, than are childhood factors such as GMA.

  • 3715. Wurdak, Mara
    et al.
    Kuntsche, Emmanuel
    Kraus, Ludwig
    Stockholm University, Faculty of Social Sciences, Centre for Social Research on Alcohol and Drugs (SoRAD). IFT Institut für Therapieforschung, München, Germany.
    Wolstein, Jörg
    Effectiveness of a brief intervention with and without booster session for adolescents hospitalized due to alcohol intoxication2016In: Journal of Substance Use, ISSN 1465-9891, E-ISSN 1475-9942, Vol. 21, no 1, p. 72-77Article in journal (Refereed)
    Abstract [en]

    Background: The Hart-am-LimiT (HaLT) project is a brief intervention program for adolescents hospitalized due to alcohol intoxication in Germany.

    Objective: To test whether a booster session has an impact on participants’ drinking behavior compared with the standard HaLT program.

    Methods: On the morning after their admission due to alcohol intoxication, 411 adolescents in the Federal State of Bavaria were interviewed between October 2008 and January 2010 and socio-demographic data and information on previous drinking behavior were recorded (t1). Eleven to 25 months (M = 16.4) after their hospital treatment, 106 adolescents completed an online questionnaire (t2).

    Results: Subgroup analysis (ANOVA with repeated measurements) indicated that adolescents who took part in the booster session did not increase episodic heavy drinking (EHD; t1: M = 1.68 EHD d; t2: 1.59 EHD d) in contrast to the non-participating group (t1: M = 1.08 d EHD; t2: 2.66 d EHD; F = 4.383, p = 0.039).

    Conclusion: Considering the study’s limitations (e.g. no randomization, low response rate, etc.), the results indicate a positive effect of a booster session following a brief intervention for adolescents who have been treated in hospital due to alcohol intoxication. Adolescents should therefore be motivated and encouraged to participate in booster sessions.

  • 3716. Wändell, Per E.
    et al.
    Gigane, Bruna
    Nixon Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Carlsson, Axel C.
    Gender Differences Regarding Novel Biomarkers and Metabolic Risk Factors in Metformin Treated Type 2 Diabetic Patients2012In: The Open Diabetes Journal, ISSN 1876-5246, E-ISSN 1876-5246, Vol. 5, p. 13-19Article in journal (Refereed)
    Abstract [en]

    We aimed to analyze associations between adiponectin, ghrelin and leptin with anthropometric and metabolic markers in men and women with Metformin-treated type 2 diabetes (n=53), recruited from a trial of relaxation therapies. Anthropometrical measures and fasting blood samples were assessed on three occasions: at baseline, and after 10 and 24 weeks: BMI, waist, HbA1c, insulin, glucose, adiponectin, leptin, fasting ghrelin, high sensitivity C-reactive protein (CRP), tumor necrosis factor α (TNF- α) and interleukin 6 (IL-6). HOMA2ir and HOMA2s were calculated from fasting glucose and insulin, and adiponectin/leptin and adiponectin/HOMA2ir ratios were calculated. In men, higher leptin and lower adiponectin/leptin ratio correlated with insulin and insulin resistance, and in women lower ghrelin with insulin and insulin resistance. In multivariate linear regression, higher levels of leptin were associated with insulin resistance among men, but not among women. Among women, insulin resistance was associated with lower adiponectin/leptin ratio and ghrelin. Factor analysis showed that leptin in women was closely related to anthropometric variables, but in men both related to anthropometric and inflammatory variables. Gender differences could indicate different pathophysiologic mechanisms of insulin resistance and type 2 diabetes among men and women, where leptin possibly could be a better marker among men, and ghrelin among women.

  • 3717.
    Wåhlin, Erik
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Dosimetric pre-treatment verification with an electronic portal imaging device2006Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    A commercially available amorphous silicon electronic portal imaging device (EPID) was studied with regard to its dosimetric properties and to determine its usefulness as a tool for dosimetric pre-treatment verification of radiotherapy treatment fields. The dosimetric properties that were studied include reproducibility over time, linearity with dose, dose rate dependence and ghosting effects. The pre-treatment verification is performed by acquiring dosimetric images with the EPID and comparing these images with predicted images, calculated by the treatment planning system. This method for verification was evaluated. Also, the calibration and configuration of the treatment planning system and of the EPID for dosimetric verification was performed and is presented here.

    The dosimetric properties of the EPID were found to be suitable for the measurements for which it is intended. It is linear with dose and does not show significant dose rate dependence or ghosting effects. As a pre-treatment verification system it is accurate within 3% and 3mm for ~99% of a region around the irradiated area of the image.

  • 3718. Xi, Bo
    et al.
    Zhang, Meixian
    Zhang, Tao
    Liang, Yajun
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Jining Medical University, China.
    Li, Shuangshuang
    Steffen, Lyn M.
    Hypertension Screening Using Blood Pressure to Height Ratio2014In: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 134, no 1, p. E106-E111Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The definition of hypertension in children is too complex to be used by medical professionals and children and their parents because of the age-, gender-, and height-specific blood pressure (BP) algorithm. The aim of this study was to simplify the pediatric BP percentile references using BP to height ratio (BPHR, equal to BP/height) for screening for prehypertension and hypertension in Chinese children. METHODS: Data were obtained from the China Health and Nutrition Survey, which was conducted from 1991 to 2009 and included 11 661 children aged 6 to 17 years with complete data on age, gender, height, and BP values. Receiver operating characteristic curve analysis was performed to assess the performance of systolic BPHR (SBPHR) and diastolic BPHR (DBPHR) for screening for pediatric prehypertension and hypertension. RESULTS: The optimal thresholds for defining prehypertension were 0.81 in children aged 6 to 11 years and 0.70 in adolescents aged 12 to 17 years for SBPHR and 0.52 in children and 0.46 in adolescents for DBPHR, respectively. The corresponding values for hypertension were 0.84, 0.78, 0.55, and 0.50, respectively. The negative predictive values were much higher (all >= 99%) for prehypertension and hypertension, although the positive predictive values were relatively lower, ranging from 13% to 75%. CONCLUSIONS: BPHR index is simple and accurate for screening for prehypertension and hypertension in Chinese children aged 6 to 17 years and can be used for early screening or treating Chinese children with hypertension.

  • 3719. Xu, Junfang
    et al.
    Wang, Jian
    Wimo, Anders
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Qiu, Chengxuan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    The economic burden of dementia in China, 1990-2030: implications for health policy2017In: Bulletin of the World Health Organization, ISSN 0042-9686, E-ISSN 1564-0604, Vol. 95, no 1, p. 18-26Article in journal (Refereed)
    Abstract [en]

    Objective To quantify and predict the economic burden of dementia in China for the periods 1990-2010 and 2020-2030, respectively, and discuss the potential implications for national public health policy. Methods Using a societal, prevalence-based, gross cost-of-illness approach and data from multiple sources, we estimated or predicted total annual economic costs of dementia in China. We included direct medical costs in outpatient and inpatient settings, direct non-medical costs - e.g. the costs of transportation and indirect costs due to loss of productivity. We excluded comorbidity-related costs. Findings The estimated total annual costs of dementia in China increased from 0.9 billion United States dollars (US$) in 1990 to US$47.2 billion in 2010 and were predicted to reach US$ 69.0 billion in 2020 and US$ 114.2 billion in 2030. The costs of informal care accounted for 94.4%, 92.9% and 81.3% of the total estimated costs in 1990,2000 and 2010, respectively. In China, population ageing and the increasing prevalence of dementia were the main drivers for the increasing predicted costs of dementia between 2010 and 2020, and population ageing was the major factor contributing to the growth of dementia costs between 2020 and 2030. Conclusion In China, demographic and epidemiological transitions have driven the growth observed in the economic costs of dementia since the 1990s. If the future costs of dementia are to be reduced, China needs a nationwide dementia action plan to develop an integrated health and social care system and to promote primary and secondary prevention.

  • 3720.
    Xu, Junfang
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Shandong University, China.
    Wang, Jian
    Wimo, Anders
    Qiu, Chengxuan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    The economic burden of mental disorders in China, 2005-2013: implications for health policy2016In: BMC Psychiatry, ISSN 1471-244X, E-ISSN 1471-244X, Vol. 16, article id 137Article in journal (Refereed)
    Abstract [en]

    Background: Mental disorders represent a major contributor to disease burden worldwide. We sought to quantify the national economic burden of mental disorders in China. Methods: We used a prevalence-based, bottom-up approach to estimate the economic costs of mental disorders in 2005-2013 in China. Prevalence data were derived from a national survey. Cost data were derived from the electronic health records of two psychiatric hospitals that consisted of 25,289 outpatients (10 %) and inpatients (90 %) who were diagnosed with a mental disorder. Cost items included direct medical costs, direct non-medical costs, and indirect costs. Results: The total annual costs of mental disorders in China increased from $ 1,094.8 in 2005 to $ 3,665.4 in 2013 for individual patients, and from $ 21.0 billion to $ 88.8 billion for the whole society. The total costs of mental disorders in 2013 accounted for more than 15 % of the total health expenditure in China, and 1.1 % of China's gross domestic product. If the needs of the professional care for all patients with mental illnesses were fully met, the potential economic costs would have been almost five times higher than the actual estimated costs. Conclusions: Mental disorders imposed a huge economic burden on individuals and the society in China. A nation-wide strategic action plan for preventing mental disorders and promoting mental health and well-being is in urgent need to reduce the individual and societal costs of mental illnesses.

  • 3721.
    Xu, Lili
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute, Immunology.
    Zheng, Xiaoying
    Berzins, Klavs
    Stockholm University, Faculty of Science, The Wenner-Gren Institute, Immunology.
    Chaudhuri, Asok
    Cytokine dysregulation associated with malarial anemia in Plasmodium yoelii infected mice2013In: American Journal of Translational Research, ISSN 1943-8141, E-ISSN 1943-8141, Vol. 5, no 2, p. 235-245Article in journal (Refereed)
    Abstract [en]

    The mechanisms of malaria anemia remain incompletely understood although much effort has been put on studies in both human and murine systems. Hematopoiesis is regulated by the proliferation, differentiation and maturation of erythropoietic progenitor cells into erythrocytes and is tightly controlled by a complex communication network of cytokines as signal mediators. The present study used the murine P. yoelii 17XNL malaria model to investigate the profile of cytokines and leukocytes throughout the entire infection. Moreover, malaria induced anemia was studied in comparison with anemia induced by hemorrhage and hemolysis. During the P. yoelii infection, the levels of erythropoietic-related cytokines, such as G-CSF, GMCSF, IL-7, and IL-17, were pronouncedly reduced, while those of regulatory cytokines, such as IL-10 and TNF-alpha, were constantly increased. This cytokine profile corresponded well with the cellular composition during the infection, such as drastically decreased levels of CD4(+) and CD8(+) T cells. The profiles of erythropoiesis or hematopoiesis related cytokines during malarial anemia showed striking differences from those during anemia induced by hemorrhage or hemolysis. This study demonstrates that a markedly dysregulated cytokine network occurred in this murine malaria model, which may open a new window of insight into the mechanisms of malaria related anemia.

  • 3722.
    Xu, Tianwei
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. University of Copenhagen, Denmark.
    Magnusson Hanson, Linda L.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Lange, Theis
    Starkopf, Liis
    Westerlund, Hugo
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Madsen, Ida E. H.
    Rugulies, Reiner
    Pentti, Jaana
    Stenholm, Sari
    Vahtera, Jussi
    Hansen, Åse M.
    Kivimäki, Mika
    Rod, Naja H.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. University of Copenhagen, Denmark.
    Workplace bullying and violence as risk factors for type 2 diabetes: a multicohort study and meta-analysis2018In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, no 1, p. 75-83Article in journal (Refereed)
    Abstract [en]

    AIMS/HYPOTHESIS: The aim of this multicohort study was to examine whether employees exposed to social stressors at work, such as workplace bullying and violence, have an increased risk of type 2 diabetes.

    METHODS: The study included 45,905 men and women (40-65 years of age and free of diabetes at baseline) from four studies in Sweden, Denmark and Finland. Workplace bullying and violence were self-reported at baseline. Incident diabetes was ascertained through national health and medication records and death registers. Marginal structural Cox models adjusted for age, sex, country of birth, marital status and educational level were used for the analyses.

    RESULTS: Nine per cent of the population reported being bullied at work and 12% were exposed to workplace violence or threats of violence. Bullied participants had a 1.46 (95% CI 1.23, 1.74) times higher risk of developing diabetes compared with non-bullied participants. Exposure to violence or threats of violence was also associated with a higher risk of diabetes (HR 1.26 [95% CI 1.02, 1.56]). The risk estimates attenuated slightly when taking BMI into account, especially for bullying. The results were similar for men and women, and were consistent across cohorts.

    CONCLUSIONS/INTERPRETATION: We found a higher risk of incident type 2 diabetes among employees exposed to bullying or violence in the workplace. Further research is needed to determine whether policies to reduce bullying and violence at work may reduce the incidence of type 2 diabetes in working populations. Research on the mechanisms is also highly warranted.

  • 3723.
    Xu, W. L.
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Atti, A. R.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Gatz, M.
    Pedersen, N. L.
    Johansson, B.
    Fratiglioni, L.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Midlife overweight and obesity increase late-life dementia risk: a population-based twin study2011In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 76, no 18, p. 1568-1574Article in journal (Refereed)
    Abstract [en]

    Objective: The relation of overweight to dementia is controversial. We aimed to examine the association of midlife overweight and obesity with dementia, Alzheimer disease (AD), and vascular dementia (VaD) in late life, and to verify the hypothesis that genetic and early-life environmental factors contribute to the observed association.

    Methods: From the Swedish Twin Registry, 8,534 twin individuals aged ≥65 (mean age 74.4) were assessed to detect dementia cases (DSM-IV criteria). Height and weight at midlife (mean age 43.4) were available in the Registry. Data were analyzed as follows: 1) unmatched case-control analysis for all twins using generalized estimating equation (GEE) models and 2) cotwin matched case-control approach for dementia-discordant twin pairs by conditional logistic regression taking into account lifespan vascular disorders and diabetes.

    Results: Among all participants, dementia was diagnosed in 350 subjects, and 114 persons had questionable dementia. Overweight (body mass index [BMI] >25-30) and obesity (BMI >30) at midlife were present in 2,541 (29.8%) individuals. In fully adjusted GEE models, compared with normal BMI (20-25), overweight and obesity at midlife were related to dementia with odds ratios (ORs) (95% CIs) of 1.71 (1.30-2.25) and 3.88 (2.12-7.11), respectively. Conditional logistic regression analysis in 137 dementia-discordant twin pairs led to an attenuated midlife BMI-dementia association. The difference in ORs from the GEE and the matched case-control analysis was statistically significant (p = 0.019).

    Conclusions: Both overweight and obesity at midlife independently increase the risk of dementia, AD, and VaD. Genetic and early-life environmental factors may contribute to the midlife high adiposity-dementia association.

  • 3724.
    Xu, Wei-Li
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Caracciolo, Barbara
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Wang, Hui-Xin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Santoni, Giola
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Winblad, Bengt
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Accelerated Progression from Mild Cognitive Impairment to Dementia Among APOE epsilon 4 epsilon 4 Carriers2013In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 33, no 2, p. 507-515Article in journal (Refereed)
    Abstract [en]

    The impact of APOE ε4 on mild cognitive impairment (MCI) and its progression to dementia remain controversial. We aimed to examine the association of APOE ε4 with MCI, and to verify the hypothesis that ε4 accelerates progression from MCI to dementia. In the Kungsholmen project, 756 cognitively healthy participants and 212 people with MCI aged ≥75 years were identified at baseline. Amnestic MCI (aMCI) and other cognitive impairment no dementia (oCIND) as two subtypes of MCI were assessed based on standard definitions. The two cohorts were followed for 9 years to detect incident cases of MCI and dementia following international criteria. APOE genotypes were assessed at baseline. Data were analyzed using Cox models. During the follow-up, in the cognitively healthy cohort, 165 people developed MCI (40 aMCI and 125 oCIND) and 176 developed dementia; in the MCI cohort, 118 persons progressed to dementia. Compared with APOE ε3ε3, the hazard ratios (HRs) (95% CIs) of ε2ε4/ε3ε4 were 2.24 (1.10-4.57) for aMCI and 1.78 (1.15-2.75) for oCIND, while the ε4ε4 was related to dementia with a HR of 4.35 (1.97-9.63) in the cognitively healthy cohort. In the MCI cohort, the ε4ε4 genotype led to a multi-adjusted HR of 2.89 (1.12-7.48) for dementia and accelerated the progression to dementia by 3.36 years. The APOE ε4 heterozygotes are associated with an increased risk of aMCI and oCIND. The ε4 homozygote substantially accelerates progression from MCI to dementia, and anticipate dementia occurrence by more than 3 years in people with MCI.

  • 3725.
    Xu, Weili
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Caracciolo, Barbara
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Wang, Hui-Xin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Winblad, Bengt
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Qiu, Chengxuan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Accelerated progression from mild cognitive impairment to dementia in people with diabetes2010In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 59, no 11, p. 2928-35Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The effect of diabetes on mild cognitive impairment (MCI) and its conversion to dementia remains controversial. We sought to examine whether diabetes and pre-diabetes are associated with MCI and accelerate the progression from MCI to dementia.

    RESEARCH DESIGN AND METHODS: In the Kungsholmen Project, 963 cognitively intact participants and 302 subjects with MCI (120 with amnestic MCI [aMCI] and 182 with other cognitive impairment no dementia [oCIND]) age ≥ 75 years were identified at baseline. The two cohorts were followed for 9 years to detect the incident MCI and dementia following international criteria. Diabetes was ascertained based on a medical examination, hypoglycemic medication use, and random blood glucose level ≥ 11.0 mmol/l. Pre-diabetes was defined as random blood glucose level of 7.8-11.0 mmol/l in diabetes-free participants. Data were analyzed using standard and time-dependent Cox proportional-hazards models.

    RESULTS: During the follow-up period, in the cognitively intact cohort, 182 people developed MCI (42 aMCI and 140 oCIND), and 212 developed dementia. In the MCI cohort, 155 subjects progressed to dementia, the multi-adjusted hazard ratio (95% CI) of dementia was 2.87 (1.30-6.34) for diabetes, and 4.96 (2.27-10.84) for pre-diabetes. In a Kaplan-Meier survival analysis, diabetes and pre-diabetes accelerated the progression from MCI to dementia by 3.18 years. Diabetes and pre-diabetes were neither cross-sectionally nor longitudinally associated with MCI.

    CONCLUSIONS: Diabetes and pre-diabetes substantially accelerate the progression from MCI to dementia, and anticipate dementia occurrence by more than 3 years in people with MCI. The association of diabetes with the development of MCI is less evident in old people.

  • 3726.
    Xu, Wei-Li
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Tianjin Medical University, China.
    Pedersen, Nancy L.
    Keller, Lina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Karolinska Institutet, Sweden.
    Kalpouzos, Gregoria
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Wang, Hui-Xin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Graff, Caroline
    Winblad, Bengt
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Karolinska Institutet, Sweden.
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm Gerontology Research Center, Sweden.
    HHEX_23 AA Genotype Exacerbates Effect of Diabetes on Dementia and Alzheimer Disease: A Population-Based Longitudinal Study2015In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 12, no 7Article in journal (Refereed)
    Abstract [en]

    Background Research has suggested that variations within the IDE/HHEX gene region may underlie the association of type 2 diabetes with Alzheimer disease (AD). We sought to explore whether IDE genes play a role in the association of diabetes with dementia, AD, and structural brain changes using data from two community-based cohorts of older adults and a subsample with structural MRI. Methods and Findings The first cohort, which included dementia-free adults aged >= 75 y (n = 970) at baseline, was followed for 9 y to detect incident dementia (n = 358) and AD (n = 271) cases. The second cohort (for replication), which included 2,060 dementia-free participants aged >= 60 y at baseline, was followed for 6 y to identify incident dementia (n = 166) and AD (n = 121) cases. A subsample (n = 338) of dementia-free participants from the second cohort underwent MRI. HHEX_23 and IDE_9 were genotyped, and diabetes (here including type 2 diabetes and prediabetes) was assessed. In the first cohort, diabetes led to an adjusted hazard ratio (HR) of 1.73 (95% CI 1.19-2.32) and 1.66 (95% CI 1.06-2.40) for dementia and AD, respectively, among all participants. Compared to people carrying the GG genotype without diabetes, AA genotype carriers with diabetes had an adjusted HR of 5.54 (95% CI 2.407.18) and 4.81 (95% CI 1.88-8.50) for dementia and AD, respectively. There was a significant interaction between HHEX_23-AA and diabetes on dementia (HR 4.79, 95% CI 1.63-8.90, p = 0.013) and AD (HR 3.55, 95% CI 1.45-9.91, p = 0.025) compared to the GG genotype without diabetes. In the second cohort, the HRs were 1.68 (95% CI 1.04-2.99) and 1.64 (1.02-2.33) for the diabetes-AD and dementia-AD associations, respectively, and 4.06 (95% CI 1.06-7.58, p = 0.039) and 3.29 (95% CI 1.02-8.33, p = 0.044) for the interactions, respectively. MRI data showed that HHEX_23-AA carriers with diabetes had significant structural brain changes compared to HHEX_23-GG carriers without diabetes. No joint effects of IDE_9 and diabetes on dementia were shown. As a limitation, the sample sizes were small for certain subgroups. Conclusions A variant in the HHEX_23 gene interacts with diabetes to be associated with a substantially increased risk of dementia and AD, and with structural brain changes among dementia-free elderly people.

  • 3727.
    Xu, Weili
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Tianjin Medical University, China.
    Zhang, Hua
    Paillard-Borg, Stephanie
    Zhu, Hong
    Qi, Xiuying
    Rizzuto, Debora
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Prevalence of Overweight and Obesity among Chinese Adults: Role of Adiposity Indicators and Age2016In: Obesity Facts, ISSN 1662-4025, E-ISSN 1662-4033, Vol. 9, no 1, p. 17-28Article in journal (Refereed)
    Abstract [en]

    Objectives: The role of different body fat indicators and age in assessing the prevalence of obesity is unclear. We aimed to examine to what extent different body fat indicators including BMI, waist circumference (WC) and waist-to-hip ratio (WHR) affect the prevalence of overweight and obesity among Chinese adults taking age into account. Methods: This population-based cross-sectional study included a random sample of 7,603 adults aged 20-79 years across entire Tianjin, China. BMI, WC, and WHR were used to define overweight and obesity following standard criteria. Prevalence rates were calculated and standardized using local age-and gender-specific census data. Logistic regression was used in data analysis. Results: Using the combination of BMI, WC, and WHR, the prevalence of overweight and obesity was 69.8%, and increased with age till the age of 60 and a decline thereafter. The prevalence of overweight assessed by BMI was higher than that assessed by WC and WHR, while the prevalence of obesity defined by BMI was much lower than that defined by WC or WHR. Conclusion: The prevalence of overweight and obesity is about 70% among Chinese adults. Adiposity indicators and age play an important role in the prevalence of overweight and obesity.

  • 3728. Xu, Z.
    et al.
    Qi, X.
    Dahl, A. K.
    Xu, W.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Tianjin Medical University, China.
    Waist-to-height ratio is the best indicator for undiagnosed Type 2 diabetes2013In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 30, no 6, p. e201-E207Article in journal (Refereed)
    Abstract [en]

    Aims

    Early detection of diabetes is important for the prevention of diabetic complications. The best adiposity index for indicating Type 2 diabetes mellitus remains unclear. We aimed to identify the optimal adiposity measure among BMI, waist circumference, waist–hip ratio and waist-to-height ratio to indicate undiagnosed Type 2 diabetes and impaired fasting glucose in Chinese adults.

    Methods

    A total of 7567 participants aged 20–79 years were included in this study. Impaired fasting glucose was defined as a fasting plasma glucose level of 6.1–6.9 mmol/l in participants without diabetes. Undiagnosed Type 2 diabetes was identified as fasting plasma glucose ≥ 7.0 mmol/l when neither a history of diabetes nor use of hypoglycaemic drugs was present. Body weight, height, waist and hip circumferences were measured following standard procedures. Data were analysed using logistic regression and areas under the receiver operating characteristic curves.

    Results

    Of the 7567 participants, 536 were defined as having impaired fasting glucose and 690 were patients with Type 2 diabetes, including 290 (3.8%) persons with undiagnosed diabetes. In multivariate logistic regression, the odds ratios of waist-to-height ratio (≥ 0.5) were stronger than BMI (≥ 24 kg/m2), waist circumference (≥ 85 cm in men and ≥ 80 cm in women) and waist–hip ratio (≥ 0.85) for undiagnosed Type 2 diabetes and impaired fasting glucose. Among the four indices, waist-to-height ratio ≥ 0.5 showed the largest area under the receiver operating characteristic curve for diagnosing undiagnosed Type 2 diabetes (0.725, 95% CI 0.693–0.756) and impaired fasting glucose (0.662, 95% CI 0.638–0.687).

    Conclusions

    By comparison with BMI, waist circumference and waist–hip ratio, waist-to-height ratio ≥ 0.5 may be the best indicator for undiagnosed Type 2 diabetes and impaired fasting glucose.

  • 3729. Xue, Jin
    et al.
    Marmolejo-Ramos, Fernando
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Pei, Xuna
    The linguistic context effects on the processing of body-object interaction words: An ERP study on second language learners2015In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1613, p. 37-48Article in journal (Refereed)
    Abstract [en]

    Embodied theories of cognition argue that the processing of both concrete and abstract concepts requires the activation of sensorimotor systems. The present study examined the time course for embedding a sensorimotor context in order to elicit sensitivity to the sensorimotor consequences of understanding body-object interaction (BOI) words. In the study, Event-Related Potentials (ERPs) were recorded while subjects performed a sentence acceptability task. Target BOI words were preceded by rich or poor sensorimotor sentential contexts. The behavioural results replicated previous findings in that high BOI words received a response faster than low BOI words. In addition to this, however, there was a context effect in the sensorimotor region as well as a BOI effect in the parietal region (involved in object representation). The results indicate that the sentential sensorimotor context contributes to the subsequent BOI processing and that action-and perception-related language leads to the activation of the same brain areas, which is consistent with the embodiment theory.

  • 3730.
    Yacoub, Chahed
    Stockholm University, Faculty of Science, Department of Physics. Linköping University, Sweden.
    Measurement of absorbed dose to the skin and its relation with microcircular changes in breast cancer radiotherapy2016Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Radiation therapy has been shown to increase local and regional control as well as overall survival with breast cancer, but the vast majority of patients develop acute skin reactions, which are in part related to microvascular changes. These reactions vary between different skin sites. The aim of this work is to determine the absorbed dose to the skin by measurements and investigate if there is a correlation between the absorbed dose at different areas of the breast and the local changes in microcirculation in the skin after breast cancer radiotherapy. The study includes characterisation of the Gafchromic EBT3 film and Epson Perfection V600 Photo scanner which are used for absorbed dose determination. The measurements were done both on an anthropomorphic female phantom and on a patient undergoing breastcancer radiotherapy. Twenty-one pieces of film (2x1 cm2) were placed on the surface ofthe breast (both for the phantom and patient) and irradiated with a prescribed dose to the target of 2.66 Gy with two opposed fields using 6 MV beam. It was observed that mainly 45-64 % of the prescribed dose was deposited at the surface, both for the phantom and patient. Using laser speckle contrast imaging and polarised light spectroscopy, the regional changes in mean blood perfusion and in mean red blood cell concentration (RBCC) at the end of the treatment with a total prescribed dose of 42.6 Gy, compared to baseline, were measured in both the treated and untreated breast of the same patient. Although marked increases in perfusion were seen in different areas of the treated breast, there was no signicant correlation between the changes in perfusion and the absorbed dose at these areas. However, a statistical correlation was found between the changes in RBCC and the absorbed skin dose at the same areas. To further elucidate the relation between the changes in skin microcirculation and the absorbed radiation dose during breast cancer radiotherapy, future studies using a larger number of patients are needed.

  • 3731.
    Yacoub, Chahed
    Stockholm University, Faculty of Science, Department of Physics.
    Measurement of absorbed dose to the skin and its relation with microcircular changes in breast cancer radiotherapy2016Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Radiation therapy has been shown to increase local and regional control as well as overall

    survival with breast cancer, but the vast majority of patients develop acute skin reactions,

    which are in part related to microvascular changes. These reactions vary between different

    skin sites. The aim of this work is to determine the absorbed dose to the skin by measurements

    and investigate if there is a correlation between the absorbed dose at different areas of

    the breast and the local changes in microcirculation in the skin after breast cancer radiotherapy.

    The study includes characterisation of the Gafchromic EBT3 film and Epson Perfection

    V600 Photo scanner which are used for absorbed dose determination. The measurements

    were done both on an anthropomorphic female phantom and on a patient undergoing breast

    cancer radiotherapy. Twenty-one pieces offilm (2x1 cm2) were placed on the surface of

    the breast (both for the phantom and patient) and irradiated with a prescribed dose to the

    target of 2.66 Gy with two opposed fields using 6 MV beam.

    It was observed that mainly 45-64 % of the prescribed dose was deposited at the surface,

    both for the phantom and patient. Using laser speckle contrast imaging and polarised light

    spectroscopy, the regional changes in mean blood perfusion and in mean red blood cell

    concentration (RBCC) at the end of the treatment with a total prescribed dose of 42.6

    Gy, compared to baseline, were measured in both the treated and untreated breast of the

    same patient. Although marked increases in perfusion were seen in different areas of the

    treated breast, there was no significant correlation between the changes in perfusion and

    the absorbed dose at these areas. However, a statistical correlation was found between the

    changes in RBCC and the absorbed skin dose at the same areas. To further elucidate the

    relation between the changes in skin microcirculation and the absorbed radiation dose during

    breast cancer radiotherapy, future studies using a larger number of patients are needed.

  • 3732. Yan, Weirong
    et al.
    Palm, Lars
    Lu, Xin
    Stockholm University, Faculty of Social Sciences, Department of Sociology. Karolinska Institutet.
    Nie, Shaofa
    Xu, Biao
    Zhao, Qi
    Tao, Tao
    Cheng, Liwei
    Tan, Li
    Dong, Hengjin
    Diwan, Vinod K.
    ISS - An Electronic Syndromic Surveillance System for Infectious Disease in Rural China2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 4, p. e62749-Article in journal (Refereed)
    Abstract [en]

    Background: syndromic surveillance system has great advantages in promoting the early detection of epidemics and reducing the necessities of disease confirmation, and it is especially effective for surveillance in resource poor settings. However, most current syndromic surveillance systems are established in developed countries, and there are very few reports on the development of an electronic syndromic surveillance system in resource-constrained settings. Objective: this study describes the design and pilot implementation of an electronic surveillance system (ISS) for the early detection of infectious disease epidemics in rural China, complementing the conventional case report surveillance system. Methods: ISS was developed based on an existing platform 'Crisis Information Sharing Platform' (CRISP), combining with modern communication and GIS technology. ISS has four interconnected functions: 1) work group and communication group; 2) data source and collection; 3) data visualization; and 4) outbreak detection and alerting. Results: As of Jan. 31st 2012, ISS has been installed and pilot tested for six months in four counties in rural China. 95 health facilities, 14 pharmacies and 24 primary schools participated in the pilot study, entering respectively 74256, 79701, and 2330 daily records into the central database. More than 90% of surveillance units at the study sites are able to send daily information into the system. In the paper, we also presented the pilot data from health facilities in the two counties, which showed the ISS system had the potential to identify the change of disease patterns at the community level. Conclusions: The ISS platform may facilitate the early detection of infectious disease epidemic as it provides near real-time syndromic data collection, interactive visualization, and automated aberration detection. However, several constraints and challenges were encountered during the pilot implementation of ISS in rural China.

  • 3733. Yan, Xin
    et al.
    Wang, Zhen
    Westberg-Rasmussen, Sidse
    Tarbier, Marcel
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Rathjen, Thomas
    Tattikota, Sudhir G.
    Peck, Bailey C. E.
    Kanke, Matt
    Oxvig, Claus
    Frystyk, Jan
    Starup-Linde, Jakob
    Sethupathy, Praveen
    Friedländer, Marc R.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Gregersen, Søren
    Poy, Matthew N.
    Differential Impact of Glucose Administered Intravenously and Orally on Circulating miR-375 Levels in Human Subjects2017In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 102, no 10, p. 3749-3755Article in journal (Refereed)
    Abstract [en]

    Background

    To date, numerous nucleic acid species have been detected in the systemic circulation including microRNAs (miRNAs); however, their functional role in this compartment remains unclear.

    Objective

    The aim of this study was to determine whether systemic levels of miRNAs abundant in blood, including the neuroendocrine tissue-enriched miR-375, are altered in response to a glucose challenge.

    Design

    Twelve healthy males were recruited for an acute crossover study that consisted of two tests each following an 8-hour fasting period. An oral glucose tolerance test (OGTT) was performed, and blood samples were collected over a 3-hour period. Following a period of at least 1 week, the same participants were administered an isoglycemic intravenous glucose infusion (IIGI) with the same blood-collection protocol.

    Results

    The glucose response curve following the IIGI mimicked that obtained after the OGTT, but as expected, systemic insulin levels were lower during the IIGI compared with the OGTT (P < 0.05). miR-375 levels in circulation were increased only in response to an OGTT and not during an IIGI. In addition, the response to the OGTT also coincided with the transient increase of circulating glucagon-like peptide (GLP)-1, GLP-2, and glucose-dependent insulinotropic polypeptide.

    Conclusions

    The present findings show levels of miR-375 increase following administration of an OGTT and, in light of its enrichment in cells of the gut, suggest that the gastrointestinal tract may play an important role in the abundance and function of this miRNA in the blood.

  • 3734. Yan, Z.
    et al.
    Liang, Yajun
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Jining Medical University, China.
    Shi, J.
    Cai, C.
    Jiang, H.
    Song, A.
    Qiu, Chengxuan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Carotid stenosis and cognitive impairment amongst older Chinese adults living in a rural area: a population-based study2016In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 23, no 1, p. 201-204Article in journal (Refereed)
    Abstract [en]

    Background and purpose: The possible association between carotid stenosis and cognitive impairment in the Chinese population has been rarely investigated. The association between the severity of carotid stenosis and cognitive impairment amongst older Chinese people living in a rural area was assessed.

    Methods: This cross-sectional study included 1375 participants (age >= 60 years) from the Confucius Hometown Aging Project in Shandong. In 2010-2011, data were collected through interviews and clinical examinations. Carotid stenosis was assessed using ultrasonography. Cognitive impairment was defined according to the education-specific cutoff scores of the Mini-Mental State Examination. Data were analyzed using multinomial logistic models.

    Results: The overall prevalence was 7.0% for moderate carotid stenosis, 2.0% for severe stenosis and 6.0% for cognitive impairment. The multi-adjusted odds ratio of cognitive impairment was 1.43 (95% confidence interval 0.63-3.22) for moderate carotid stenosis and 3.75 (1.24-11.40) for severe carotid stenosis (P-trend = 0.023). Similar results were obtained in people without a history of cerebrovascular disease.

    Conclusions: Severe carotid stenosis, even asymptomatic, is associated with cognitive impairment independent of atherosclerotic risk factors and disorders amongst older Chinese people.

  • 3735. Yan, Zhongrui
    et al.
    Liang, Yajun
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Chinese Academy of Medical Sciences, People's Republic of China.
    Jiang, Hui
    Cai, Chuanzhu
    Sun, Binglun
    Qiu, Chengxuan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Metabolic Syndrome and Subclinical Carotid Atherosclerosis Among Chinese Elderly People Living in a Rural Community2014In: Metabolic Syndrome and Related Disorders, ISSN 1540-4196, E-ISSN 1557-8518, Vol. 12, no 5, p. 269-276Article in journal (Refereed)
    Abstract [en]

    Background: The relationship between the metabolic syndrome and subclinical atherosclerosis among elderly people remains controversial. We seek to investigate the associations of metabolic syndrome and its components with subclinical carotid atherosclerosis in older people living in rural China. Methods: This cross-sectional study included 911 participants (age >= 60 years, 59.4% women) of the community-based Confucius Hometown Aging Project in Shandong, China, who were free of clinical cardiovascular disease. In 2010-2011, data were collected through interviews, clinical examinations, and laboratory tests. Carotid intima media thickness (cIMT) and carotid artery plaque were assessed using ultrasonography. Metabolic syndrome was defined by four sets of criteria. Data were analyzed with multiple general linear and logistic regression models. Results: Carotid plaque was detected in 514 (56.4%) persons. Depending on the defining criteria, prevalence of metabolic syndrome ranged from 30.6% to 56.9%. Hypertension, elevated blood pressure (>= 130/85 mmHg), diabetes/prediabetes, and high fasting plasma glucose (>= 5.6 mmol/L) were significantly associated with an increased likelihood of carotid plaque, whereas an increased cIMT was associated with elevated blood pressure and hypertension (P < 0.05). Obesity, high triglycerides, and dyslipidemia were not associated with carotid artery plaque or cIMT. The significant association of metabolic syndrome with an increased likelihood of carotid plaque disappeared when elevated blood pressure and high plasma glucose were added to the models. Metabolic syndrome was not associated with cIMT. Conclusions: Metabolic syndrome is associated with subclinical carotid plaque among Chinese elderly people, driven primarily by elevated blood pressure and hyperglycemia. Older adults with metabolic syndrome, especially those with high blood pressure and hyperglycemia, may benefit from evaluation for subclinical atherosclerosis.

  • 3736. Yang, Lei
    et al.
    Martikainen, Pekka
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS). University of Helsinki, Finland; Max Planck Institute for Demographic Research, Germany .
    Silventoinen, Karri
    Konttinen, Hanna
    Association of socioeconomic status and cognitive functioning change among elderly Chinese people2016In: Age and Ageing, ISSN 0002-0729, E-ISSN 1468-2834, Vol. 45, no 5, p. 673-679Article in journal (Refereed)
    Abstract [en]

    Background and Objective: the inverse association between high socioeconomic status and impaired cognitive functioning in old age has been widely studied. However, it is still inconclusive whether higher socioeconomic status slows the rate of cognitive decline over ageing, especially in non-Western populations. We examined this association using a large population-based longitudinal survey of older Chinese persons. Methods: the sample came from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) (from the years 2002 to 2011, N = 15,798 at baseline, aged 65-105). The Mini-Mental State Examination (MMSE) based on face-to-face interviews was used to assess cognitive functioning. Socioeconomic status was assessed using educational attainment and household income per capita. Latent growth curve and selection model considering the attrition during the follow-up were utilised to assess the effect of socioeconomic status on the rate of change in cognitive functioning. Results: at baseline, younger elderly people, urban residents and elderly people living alone had better cognitive performance in both genders. Educational attainment was positively associated with cognitive functioning at baseline but did not have a significant effect on the rate of change in cognitive functioning. Higher incomes were associated with better cognitive functioning at baseline, but this difference diminished during the follow-up. Conclusion: higher socioeconomic status was associated with better cognitive performance at baseline but could not protect against the rate of decline in cognitive functioning measured by MMSE in this longitudinal study for elderly Chinese people.

  • 3737. Yang, Y.
    et al.
    Zhang, Y.
    Fang, L.
    Halloran, M. E.
    Ma, M.
    Liang, S.
    Kenah, E.
    Britton, Tom
    Stockholm University, Faculty of Science, Department of Mathematics.
    Chen, E.
    Hu, J.
    Tang, F.
    Cao, W.
    Feng, Z.
    Longini, I. M., Jr.
    Household transmissibility of avian influenza A (H7N9) virus, China, February to May 2013 and October 2013 to March 20142015In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 20, no 10Article in journal (Refereed)
    Abstract [en]

    To study human-to-human transmissibility of the avian influenza A (H7N9) virus in China, household contact information was collected for 125 index cases during the spring wave (February to May 2013), and for 187 index cases during the winter wave (October 2013 to March 2014). Using a statistical model, we found evidence for human-to-human transmission, but such transmission is not sustainable. Under plausible assumptions about the natural history of disease and the relative transmission frequencies in settings other than household, we estimate the household secondary attack rate (SAR) among humans to be 1.4% (95% CI: 0.8 to 2.3), and the basic reproductive number R0 to be 0.08 (95% CI: 0.05 to 0.13). The estimates range from 1.3% to 2.2% for SAR and from 0.07 to 0.12 for R0 with reasonable changes in the assumptions. There was no significant change in the human-to-human transmissibility of the virus between the two waves, although a minor increase was observed in the winter wave. No sex or age difference in the risk of infection from a human source was found. Human-to-human transmissibility of H7N9 continues to be limited, but it needs to be closely monitored for potential increase via genetic reassortment or mutation.

  • 3738. Yin, Z.
    et al.
    Fei, Z.
    Qiu, C.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Brasher, M. S.
    Kraus, V. B.
    Zhao, W.
    Shi, X.
    Zeng, Y.
    Dietary diversity and cognitive function among elderly people: A population-based study2017In: The Journal of Nutrition, Health & Aging, ISSN 1279-7707, E-ISSN 1760-4788, Vol. 21, no 10, p. 1089-1094Article in journal (Refereed)
    Abstract [en]

    To explore associations of dietary diversity with cognitive function among Chinese elderly. This cross-sectional study was conducted in 2011-2012, data were analyzed using multiple linear regression and logistic regression models. community-based setting in the 23 provinces in China. 8,571 elderly participants, including 2984 younger elderly aged 65-79 and 5587 oldest old aged 80+ participated in this study. Intake frequencies of food groups was collected and dietary diversity (DD) was assessed based on the mean of DD score. Cognitive function was assessed using the Chinese version of Mini-Mental State Examination (MMSE), and cognitive impairment was defined using education-based cutoffs. Information about socio-demographics, lifestyles, resilience and health status was also collected. Poor dietary diversity was significantly associated with cognitive function, with beta (95% CI) of -0.11(-0.14, -0.08) for - log (31-MMSE score) and odds ratio (95% CI) of 1.29 (1.14, 1.47) for cognitive impairment. Interaction effect of age with DD was observed on cognitive impairment (P interaction=0.018), but not on-log (31-MMSE score) (P interaction=0.08). Further separate analysis showed that poor DD was significantly associated with increased risk of cognitive impairment in the oldest old (p < 0.01), with odds ratio (95% CI) of 1.34 (1.17, 1.54), while not in the younger elderly (p > 0.05), with OR (95% CI) being 1.09 (0.80, 1.47) in the fully adjusted model. Similar results were obtained when DD was categorized into four groups. Poor dietary diversity was associated with worse global cognitive function among Chinese elderly, and particularly for the oldest old. This finding would be very meaningful for prevention of cognitive impairment.

  • 3739. Yin, Zhaoxue
    et al.
    Yan, Zhongrui
    Liang, Yajun
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Jining Medical University, China.
    Jiang, Hui
    Cai, Chuanzhu
    Song, Aiqin
    Feng, Lei
    Qiu, Chengxuan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Interactive effects of diabetes and impaired kidney function on cognitive performance in old age: a population-based study2016In: BMC Geriatrics, ISSN 1471-2318, E-ISSN 1471-2318, Vol. 16Article in journal (Refereed)
    Abstract [en]

    Background: The interactive effect between diabetes and impaired kidney function on cognitive impairment in older adults has not yet been reported. The aim of this study was to investigate the association of diabetes and impaired kidney function with cognitive impairment among Chinese older people living in a rural area. Methods: This cross-sectional study included 1,358 participants (age >= 60 years; 60.5 % women) in the population-based Confucius Hometown Aging Project in Shandong, China. Data on demographics, lifestyle factors, health history, use of medications, global cognitive function, and kidney function were collected through structured interviews, clinical examinations, and blood tests. We defined diabetes as a fasting plasma glucose level >= 7.0 mmol/l or use of hypoglycemic agents, impaired kidney function as glomerular filtration rate estimated from cystatin C (eGFR(cys)) <60 ml/min/1.73 m(2). Cognitive impairment was defined using the education-based cut-off scores of Mini-Mental State Examination (MMSE). Data were analyzed using multiple general linear and logistic regression models. Results: Cognitive impairment was defined in 197 (14.5 %) persons. The multi-adjusted beta coefficient of MMSE score associated with diabetes was -0.06 (95 % confidence interval [CI], -0.16, 0.03); the corresponding figures associated with eGFR(cys) <60, 60-89.9, and >= 90 ml/min/1.73 m(2) were -0.15 (-0.28, -0.02), -0.01 (-0.10, 0.08), and 0 (reference) (P-trend = 0.046), respectively. Diabetes and impaired kidney function showed an interactive effect on cognitive impairment (P-interaction = 0.02). Compared with individuals having neither diabetes nor impaired kidney function, those with both conditions had a multi-adjusted odds ratio of 4.23 (95 % CI, 2.10-8.49) for cognitive impairment. The relative excess risk due to interaction was 2.74. Conclusions: This study suggests that concurrent presence of diabetes and impaired kidney function is associated with a substantial likelihood for cognitive impairment in older adults.

  • 3740. Yngve, Moa
    et al.
    Lidström, Helene
    Ekblad, Elin
    Hemmingsson, Helena
    Stockholm University, Faculty of Social Sciences, Department of Special Education.
    Perceived need of accomodations for high school students with special educational needs2018Conference paper (Refereed)
  • 3741. Yoluk, Özge
    et al.
    Lindahl, Erik
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab). KTH Royal Institute of Technology, Sweden.
    Andersson, Magnus
    Conformational Gating Dynamics in the GluCl Anion-Selective Chloride Channel2015In: ACS Chemical Neuroscience, ISSN 1948-7193, E-ISSN 1948-7193, Vol. 6, no 8, p. 1459-1467Article in journal (Refereed)
    Abstract [en]

    Cys-loop receptors are central to propagation of signals in the nervous system. The gating of the membrane-spanning pore is triggered by structural rearrangements in the agonist-binding site, located some so A away from the pore. A sequential conformational change, propagating from the ligand-binding site to the pore, has been proposed to govern gating in all Cys-loop receptors. Here, we identify structural and dynamic components of the conformational gating in the eukaryotic glutamate-gated chloride channel (GluCl) by means of molecular dynamics (MD) simulations with and without the L-glutamate agonist bound. A significant increase in pore opening and accompanying hydration is observed in the presence of glutamate. Potential of mean force calculations reveal that the barrier for ion passage drops from 15 kcal/mol to 5-10 kcal/mol with the agonist bound. This appears to be explained by agonist binding that leads to significant changes in the intersubunit hydrogen-bonding pattern, which induce a slight tilt of the extracellular domain relative to the transmembrane domain in the simulations. This rearrangement is subtle, but correspond to the direction of the quaternary twist observed as a key difference between open and closed X-ray structures. While the full reversible gating is still a much slower process, the observed structural dynamics sheds new light on the early stages of how the agonist influences the extracellular domain, how the extracellular domain interacts with the transmembrane domain, and how changes in the transmembrane domain alter the free energy of ion passage.

  • 3742.
    Yu, Bing
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Cognitive and educational outcomes of being born small-for-gestational-age: A longitudinal study based on Stockholm Birth Cohort2016Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The aim of this study is to examine the long-term cognitive effects and educational outcomes of being born small-for-gestational-age (SGA). It also assesses whether the family’s attitude towards education modifies the effect of SGA on cognitive performance. A total of 9598 children born in 1953 and living in the Stockholm metropolitan area in 1963 were included in this study. Data were obtained from the Stockholm Birth Cohort. Multiple ordinary least square regressions analyses suggest that SGA children have lower mean verbal, spatial and numerical test scores than appropriate-for-gestational-age (AGA) children. However, these differences are small. Other results from modification analyses indicate that the effect of SGA status on cognitive performance is modified by the family’s attitude towards education. Additional logistic regression analyses suggest that the unadjusted difference in log odds of attaining higher education is largely explained by the family’s attitude towards education. The results suggest that the detrimental influences of being born SGA on some cognitive and educational outcomes are limited and may be reduced.

  • 3743.
    Yu, Bing
    et al.
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Garcy, Anthony M.
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    A longitudinal study of cognitive and educational outcomes of those born small for gestational age2018In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 107, no 1, p. 86-94Article in journal (Refereed)
    Abstract [en]

    Aim

    This study examined the long-term cognitive and educational outcomes of being born small for gestational age (SGA) and assessed whether the family's attitude towards education modified the effect of being born SGA on educational attainment.

    Methods

    We used anonymised data on 9598 individuals from the Stockholm Birth Cohort. This study focused on babies born in 1953 in the Stockholm metropolitan area, who were followed up for 50 years, and included educational data at the age of 13 and 48. Ordinary least squares regression analyses, modification analyses and logistic regression analyses were conducted.

    Results

    The findings suggested that individuals who were born SGA (n = 798) had lower mean verbal, spatial and numerical test scores than those born appropriate for gestational age (AGA) (n = 7364) and large for gestational age (n = 1436). The SGA/AGA differences were small, but statistically significant, and the effects of being born SGA on the test scores was modified by the family's attitude towards education. The findings also suggested that attaining higher education was largely, but not entirely, explained by the family's attitude towards education.

    Conclusion

    The detrimental effects of being born SGA were limited on cognitive and educational outcomes, but may have been reduced by positive family attitudes.

  • 3744.
    Zacarias, Orlando P.
    Stockholm University, Faculty of Social Sciences, Department of Computer and Systems Sciences. Eduardo Mondlane University (UEM).
    Mining Mozambique Health Data: The Case of Malaria: From Bayesian Incidence Risk to Incidence Case Predictions2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The health sector in Mozambique is piled with data, holding records of major public health diseases, such as malaria, cholera, etc. The process of scrutinizing such a mass of health data for useful information is challenging but essential for the health authorities and professionals. Statistical learning and inferential approaches can be used to provide health decision makers with appropriate tools for disease diagnosis and assessment, where the analysis is performed using Bayesian predictive techniques and data mining. The purpose of this thesis is to investigate how predictive data mining and Bayesian regression methods can be used effectively, so as to extract useful knowledge from reported malaria health data to support decision making and management. 

    In summary, effective Bayesian predictive methods based on spatial and space-time reported cases of malaria have been derived, allowing the extraction of the main risk factors for malaria. Predictive models that combine consecutive temporal connections within the analysis of the space-time variations of the disease have been found to be relevant when the explicit modeling of seasonality is not required or is even unfeasible.

    Investigation of the most effective ways to derive numerical predictive models was performed using several regression predictive methods. The conclusions are that effective numerical prediction of new cases of the disease can be achieved by training support vector machines using a time-window approach for the choice of different training sets based on a number of years and reducing the time towards the test set. The best performance is obtained for a smaller time-window. Another contribution of this thesis is the determining of the importance of predictors in the prediction of the incidence of malaria, performed by adopting the permutation accuracy strategy (from the random forests method) using the test set. Also, an additional contribution relates to a significant reduction in the predictive error, which has been obtained by the employment of a sample correction bias strategy, while testing the predictive models in different regions, other than where they were initially developed.

  • 3745.
    Zadravec, Damir
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Metabolic Significance of Fatty Acid Elongation2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Very long-chain fatty acids (VLCFAs), including polyunsaturated fatty acids (PUFAs), are essential lipids whose functional diversity is made possible by variation in their chain length and degree of unsaturation. Fatty acids can either be derived directly from the diet or they can be synthesized de novo through lipogenesis, up to 16 carbons in length by fatty acid synthase. Further elongation into VLCFAs is catalysed by the enzymes referred to as elongation of very long-chain fatty acids (ELOVLs). Seven ELOVL proteins have been identified, all of which display distinct fatty acid substrate specificity. The enclosed papers discuss issues regarding the regulation, function and contribution to lipid composition of the Elovl genes with special emphasis on Elovl2 and Elovl3.

    In primary brown adipocytes the Elovl3 gene was shown to be regulated by all three PPAR isoforms, involving both transcriptional activation and mRNA stability. In an attempt to clarify the role of ELOVL3 in whole-body lipid homeostasis, the metabolic effects associated with Elovl3 ablation in mice were investigated. Elovl3-ablated mice were lean and showed markedly reduced triglyceride and leptin levels in serum. In addition, the mice were completely resistant to diet-induced obesity, associated with a reduced hepatic lipogenic gene expression and triglyceride content.

    Over-expression of Elovl2 in cells promoted accumulation of lipid droplets, associated with enhanced fatty acid uptake and induction of PPARγ target genes. To further assess the in vivo function of ELOVL2, the Elovl2 gene was disrupted in mice by homologous recombination. Elovl2-ablated mice exhibited a severe reduction of the elongation products of C24:5n-6 in the testis, indicating a novel role of ELOVL2 in the formation of very-long-chain PUFAs ≥C26. In addition, Elovl2+/- male mice displayed both pre- and post-meiotic deficiency of spermatogenesis. These results specify an indispensable function of ELOVL2-derived fatty acids, which can give new insights into nutritional intervention as an aid in assisting male fertility problems.

  • 3746.
    Zadravec, Damir
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Physiology.
    Tvrdik, Petr
    Guillou, Hervé
    Haslam, Richard
    Kobayashi, Tsutomu
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Napier, Johnathan A
    Capecchi, Mario R
    Jacobsson, Anders
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Physiology.
    ELOVL2 controls the level of n-6 28:5 and 30:5 fatty acids in testis: a prerequisite for male fertility and sperm maturation in mice2011In: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 52, no 2, p. 245-255Article in journal (Refereed)
    Abstract [en]

    ELOVL2 is a member of the mammalian microsomal ELOVL fatty acid enzyme family, involved in the elongation of very long-chain fatty acids including PUFAs required for various cellular functions in mammals. Here, we used ELOVL2-ablated (Elovl2(-/-)) mice to show that the PUFAs with 24-30 carbon atoms of the ω-6 family in testis are indispensable for normal sperm formation and fertility in male mice. The lack of Elovl2 was associated with a complete arrest of spermatogenesis, with seminiferous tubules displaying only spermatogonia and primary spermatocytes without further germinal cells. Furthermore, based on acyl-CoA profiling, heterozygous Elovl2(+/-) male mice exhibited haploinsufficiency, with reduced levels of C28:5 and C30:5n-6 PUFAs, which gave rise to impaired formation and function of haploid spermatides. These new insights reveal a novel mechanism involving ELOVL2-derived PUFAs in mammals and previously unrecognized roles for C28 and C30 n-6 PUFAs in male fertility. In accordance with the function suggested for ELOVL2, the Elovl2(-/-) mice show distorted levels of serum C20 and C22 PUFAs from both the n-3 and the n-6 series. However, dietary supplementation with C22:6n-3 could not restore male fertility to Elovl2(+/-) mice, suggesting that the changes in n-6 fatty acid composition seen in the testis of the Elovl2(+/-) mice, cannot be compensated by increased C22:6n-3 content.

  • 3747. Zapata, Luis
    et al.
    Susak, Hana
    Drechsel, Oliver
    Friedländer, Marc R.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Stockholm University, Science for Life Laboratory (SciLifeLab). The Barcelona Institute of Science and Technology, Spain; Universitat Pompeu Fabra (UPF), Spain.
    Estivill, Xavier
    Ossowski, Stephan
    Signatures of positive selection reveal a universal role of chromatin modifiers as cancer driver genes2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 13124Article in journal (Refereed)
    Abstract [en]

    Tumors are composed of an evolving population of cells subjected to tissue-specific selection, which fuels tumor heterogeneity and ultimately complicates cancer driver gene identification. Here, we integrate cancer cell fraction, population recurrence, and functional impact of somatic mutations as signatures of selection into a Bayesian model for driver prediction. We demonstrate that our model, cDriver, outperforms competing methods when analyzing solid tumors, hematological malignancies, and pan-cancer datasets. Applying cDriver to exome sequencing data of 21 cancer types from 6,870 individuals revealed 98 unreported tumor type-driver gene connections. These novel connections are highly enriched for chromatin-modifying proteins, hinting at a universal role of chromatin regulation in cancer etiology. Although infrequently mutated as single genes, we show that chromatin modifiers are altered in a large fraction of cancer patients. In summary, we demonstrate that integration of evolutionary signatures is key for identifying mutational driver genes, thereby facilitating the discovery of novel therapeutic targets for cancer treatment.

  • 3748. Zarina, Gunita
    et al.
    Sholts, Sabrina B.
    Tichinin, Alina
    Rudovica, Vita
    Viksna, Arturs
    Engizere, Austra
    Muiznieks, Vitolds
    Bartelink, Eric J.
    Wärmländer, Sebastian K. T. S.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. UCLA/Getty Conservation Programme, UCLA, United States.
    Cribra orbitalia as a potential indicator of childhood stress: Evidence from paleopathology, stable C, N, and O isotopes, and trace element concentrations in children from a 17th-18th century cemetery in Jekabpils, Latvia2016In: Journal of Trace Elements in Medicine and Biology, ISSN 0946-672X, E-ISSN 1878-3252, Vol. 38, p. 131-137Article in journal (Refereed)
    Abstract [en]

    Cribra orbitalia (CO), or porotic hyperostosis (PH) of the orbital roof, is one of the most common pathological conditions found in archaeological subadult skeletal remains. Reaching frequencies higher than 50% in many prehistoric samples, CO has been generally attributed to a variety of factors including malnutrition (e.g., megaloblastic anemia) and parasitism. In this study, we tested the relationship between CO, trace element concentrations, and stable isotope values (delta C-13, delta N-15, delta O-18) in subadult skeletons from a 17th to 18th century cemetery in the historic town of Jekabpils, Latvia. A total of 28 subadults were examined, seven of which (25%) showed evidence of CO. Bioarchaeological evidence indicated high mortality for children in this cemetery: half of the burials were subadults under the age of 14, while a third were under the age of four. Life expectancy at birth was estimated to have been only 21.6 years. Trace element concentrations measured by Inductively Coupled Plasma - Mass Spectrometry (ICP-MS) showed no relationship between presence or absence of CO and levels of manganese, zinc, strontium, barium, copper, cadmium, or lead in the bones (p>0.05). However, a significant correlation (p<0.05) was found between the presence of CO and decreased levels of iron. The correlations between CO and decreased levels of copper and lead approached significance (p=0.056 for both elements). Individuals with CO furthermore displayed significantly lower delta N-15 isotope values, suggesting greater consumption of lower trophic level food resources than those unaffected by CO; delta C-13 and delta O-18 values, in contrast, showed no significant differences. These results suggest that the prevalence of CO may be related to dietary deficiencies. In this case, low iron levels may also signify a diet low in other key vitamins (e.g., B-g and B-12), which are known to cause megaloblastic anemia.

  • 3749. Zerbetto, Mirco
    et al.
    Polimeno, Antonino
    Kotsyubynskyy, Dmytro
    Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry.
    Ghalebani, Leila
    Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry.
    Kowalewski, Jozef
    Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry, Department of Physical Chemistry.
    Meirovitch, Eva
    Olsson, Ulrika
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    An integrated approach to NMR spin relaxation in flexible biomolecules: Application to β-D-glucopyranosyl-(1→6)-α-D-mannopyranosyl-OMe2009In: Journal of Chemical Physics, ISSN 0021-9606, E-ISSN 1089-7690, Vol. 131, no 23, p. p234501-Article in journal (Refereed)
    Abstract [en]

    The description of the reorientational dynamics of flexible molecules is a challenging task, in particular when the rates of internal and global motions are comparable. The commonly used simple mode-decoupling models are based on the assumption of statistical independence between these motions. This assumption is not valid when the time scale separation between their rates is small, a situation that was found to arise in oligosaccharides in the context of certain internal motions. To make possible the interpretation of NMR spin relaxation data from such molecules, we developed a comprehensive approach generally applicable to flexible rotators with one internal degree of freedom. This approach integrates a stochastic description of coupled global tumbling and internal torsional motion, quantum chemical calculations of the local potential and the local geometry at the site of the restricted torsion, and hydrodynamics-based calculations of the diffusive properties. The method is applied to the disaccharide -D-Glcp-(16)--D-[6-13C]-Manp-OMe dissolved in a DMSO-d6/D2O cryosolvent. The experimental NMR relaxation parameters, associated with the 13CH2 probe residing at the glycosidic linkage, include 13C T1 and T2 and 13C-{1H} nuclear Overhauser enhancement (NOE) as well as longitudinal and transverse dipole-dipole cross-correlated relaxation rates, acquired in the temperature range of 253–293 K. These data are predicted successfully by the new theory with only the H–C–H angle allowed to vary. Previous attempts to fit these data using mode-decoupling models failed.

  • 3750. Zetterström Dahlqvist, Heléne
    et al.
    Landstedt, Evelina
    Almquist, Ylva B.
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Gillander Gådin, Katja
    A non-randomised pragmatic trial of a school-based group cognitive-behavioural programme for preventing depression in girls2017In: International Journal of Circumpolar Health, ISSN 1239-9736, E-ISSN 2242-3982, Vol. 76, article id 1396146Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate the effectiveness of the DISA-programme in preventing depressive symptoms (DS) in adolescent girls, as implemented in a real-world school setting, accounting for baseline socioeconomic and psychosocial factors, and to investigate whether the effects of these baseline variables on DS differed between intervention participants and non-participants. In this non-randomised pragmatic trial, an electronic questionnaire was disseminated in 2011 (baseline) and 2012 (follow-up) in schools in one municipality in northern Sweden. Pupils (total n=275; intervention participants identified in the questionnaire: n=53; non-participants: n=222) were 14-15 years old at baseline. The groups were compared by means of SEM. DISA could not predict differences in DS at follow-up in this real-life setting. In the overall sample, sexual harassment victimisation (SH) at baseline was associated with DS at follow-up and the estimate for SH increased in the DISA-participants compared to the overall sample.

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