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  • 3701.
    Waldén, Tomas B
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Regulatory Factors that Reveal Three Distinct Adipocytes: The Brown, the White and the Brite2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Adipose tissues have long been considered to derive from a common origin. Even the functionally different brown and white adipose tissues were generalized to share a common origin. Brown adipose tissue is a highly innervated and vascularised tissue containing multilocular and multimitochondrial brown adipocytes. Brown adipose tissue expends energy through sympathetic nervous system-mediated non-shivering thermogenesis, where uncoupling protein 1 (UCP1) is the key player. In contrast, white adipose tissue consists of unilocular white adipocytes with a main role to store energy in the form of the lipid droplet.

    We know today that this generalisation is exaggerated since adipocytes can derive from more than one origin and not only be brown or white. We and others have demonstrated that the brown adipocyte has a dermomyotomal origin and derives from the adipomyocyte, the precursor cell that can also become a myocyte, whereas white adipocytes are suggested to derive from pericytes, cells that are embedded within the vascular vessel walls. For a long time there has been evidence that energy-expending adipocytes reside within certain white adipose tissues, based on the fact that cold exposure, by switching on the sympathetic nervous system, leads to levels of UCP1 that are not detectable in mice housed at thermoneutrality. We demonstrated that these cells have a molecular signature that is distinct from brown and white adipocytes. Since these energy-expending cells reside within certain white adipose tissues, we chose to name them brite (brown in white) adipocytes. Moreover, we also identified regulatory factors that were specifically expressed in each adipocyte type, thus, facilitating the possibility to identify the three adipocytes: the brown, the white and the brite.

  • 3702. Walker, Marjorie M.
    et al.
    Talley, Nicholas J.
    Inganas, Linn
    Engstrand, Lars
    Jones, Michael P.
    Nyhlin, Henry
    Agreus, Lars
    Kjellstrom, Lars
    Ost, Ake
    Andreasson, Anna N.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Colonic spirochetosis is associated with colonic eosinophilia and irritable bowel syndrome in a general population in Sweden2015In: Human Pathology, ISSN 0046-8177, E-ISSN 1532-8392, Vol. 46, no 2, p. 277-283Article in journal (Refereed)
    Abstract [en]

    Irritable bowel syndrome (IBS) is a functional disorder defined by symptoms in the absence of overt pathology. Colonic spirochetosis (CS), defined by histologic observation of spirochetal strains of Brachyspira in colonic biopsies, is uncommon and considered of doubtful significance. We aimed to determine the prevalence of CS in the general population, identify subtle colon pathologies, and evaluate a link with symptoms of IBS. Colonoscopy was performed in 745 subjects (aged 19-70 years, mean age 51 years, 43% male) with biopsies (ileum and 4 colonic sites) from a random population sample, Stockholm, Sweden, who completed a validated questionnaire of gastrointestinal symptoms; IBS was identified by Rome III criteria. CS was identified by histology and immunohistochemistry. In a general population, 17 individuals (2.28%; 95% confidence interval, 1.2%-3.5%) were diagnosed as having CS by histology; 6 (35%) had IBS. CS was always present in the sigmoid colon, but only 14 rectal biopsies. Eosinophils were increased in colon biopsies in CS cases versus controls, in the transverse (p = .02), sigmoid colon (P = .001), and rectum (P = .0005) with subepithelial eosinophil clusters (P = .053). Lymphoid follicles (at any site) were present in 13 CS (P = .0003). There was a 3-fold increased risk of IBS in CS (odds ratio, 3.59; 95% confidence interval, 1.27-10.11; P = .015). Polyps and diverticular disease were similar in CS cases and controls. The prevalence of CS in a general population is 2% and associated with nonconstipating IBS. Colonic eosinophilia with lymphoid follicles may signify the presence of CS.

  • 3703. Walker, Marjorie M.
    et al.
    Talley, Nicholas J.
    Jones, Michael P.
    Andreasson, Anna N.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Inganas, Linn
    Nyhlin, Henry
    Agreus, Lars
    Mo2047 Spirochaetosis Is Associated With Symptoms of Irritable Bowel Syndrome (IBS) in a General Population (the Popcol Study)2013In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 144, no 5, p. S-727-S-727Article in journal (Refereed)
  • 3704. Wallby, T.
    et al.
    Hjern, Anders
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Child health care uptake among low-income and immigrant families in a Swedish county2011In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 100, no 11, p. 1495-1503Article in journal (Refereed)
    Abstract [en]

    Aim:  To study the uptake of child health care among low-income and immigrant families in the county of Uppsala, Sweden, to investigate whether these families received extra attention as proposed in the Swedish Child Health Services (CHS) state-of-the-art consensus document from the year 2000.

    Methods:  Data were collected for 25 024 infants born 1998–2006 from the database of statistics of the Child Health Care Unit in Uppsala and socio-demographic indicators from Swedish national registers. Disposable income was divided into quartiles. Country of birth of the mother was categorized into four regions with two subgroups each, mothers with or without a Swedish-born partner. Analysis was conducted by Cox regression and linear regression models.

    Results:  Small differences between Swedish vs. immigrant and high vs. low-income families were detected. Low-income mothers (RR 0.78) as well as mothers born in all country of birth regions with an immigrant partner (RR 0.28–0.95) had lower rates of participation in parental groups.

    Conclusion:  The CHS provided basic child health care to almost all infants including children in immigrant and low-income Swedish families. However, the results did not indicate that disadvantaged families received the extra attention proposed in the consensus document.

  • 3705. Wallen, Martin Benka
    et al.
    Hasson, Dan
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Theorell, Töres
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Canlon, Barbara
    The correlation between the hyperacusis questionnaire and uncomfortable loudness levels is dependent on emotional exhaustion2012In: International Journal of Audiology, ISSN 1499-2027, E-ISSN 1708-8186, Vol. 51, no 10, p. 722-729Article in journal (Refereed)
    Abstract [en]

    Objective: To validate the hyperacusis questionnaire (HQ) in different strata of emotional exhaustion (EE). Design: HQ-scores and uncomfortable loudness levels (ULLs) were assessed in 348 individuals (140 men and 208 women) with low, intermediate, and high EE-levels. Results: Four individuals (1.1%) met the critical value for hyperacusis according to the HQ. An exploratory factor analysis extracted three factors from the HQ accounting for 57.6% of the variance. Internal consistency was acceptable for all subscales and for the total score, with Crohnbach's alpha ranging from 0.65 to 0.86. When controlling for hearing loss, significant correlations between the HQ and ULLs were found on both ears in those with intermediate (right: -0.328; left: -0.320) and high EE (right: -0.349; left: -0.393), but not with low EE (right: -0.204; left: -0.196). All correlations were negative, indicating that higher HQ-scores are correlated with lower ULLs. The strongest correlations were found for the social dimension, indicating that social aspects may correspond best to audiological parameters (ULLs) of hyperacusis. Conclusions: The results emphasize the need to take other factors, such as emotional exhaustion (long-term stress), into consideration when assessing hyperacusis with a questionnaire.

  • 3706. Wallerstedt, Susanna M.
    et al.
    Belfrage, Bjoern
    Fastbom, Johan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Association between drug-specific indicators of prescribing quality and quality of drug treatment: a validation study2015In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 24, no 9, p. 906-914Article in journal (Refereed)
    Abstract [en]

    Purpose: To evaluate the concurrent validity of three European sets of drug-specific indicators of prescribing quality.

    Methods: In 200 hip fracture patients (65years), consecutively recruited to a randomized controlled study in Sahlgrenska University Hospital in 2009, quality of drug treatment at study entry was assessed according to a gold standard as well as to three drug-specific indicator sets (Swedish National Board of Health and Welfare, French consensus panel list, and German PRISCUS list). As gold standard, two specialist physicians independently assessed and then agreed on the quality for each patient, after initial screening with STOPP (Screening Tool of Older Persons' potentially inappropriate Prescriptions) and START (Screening Tool to Alert to Right Treatment).

    Results: According to the Swedish, French, and German indicator sets, 82 (41%), 54 (27%), and 43 (22%) patients had potentially inappropriate drug treatment. A total of 141 (71%) patients had suboptimal drug treatment according to the gold standard. The sensitivity for the indicator sets was 0.51 (95% confidence interval: 0.43; 0.59), 0.33 (0.26; 0.41), and 0.29 (0.22; 0.37), respectively. The specificity was 0.83 (0.72; 0.91), 0.88 (0.77; 0.94), and 0.97 (0.88; 0.99). Suboptimal drug treatment was 2.0 (0.8; 5.3), 1.9 (0.7; 5.1), and 6.1 (1.3; 28.6) times as common in patients with potentially inappropriate drug treatment according to the indicator sets, after adjustments for age, sex, cognition, residence, multi-dose drug dispensing, and number of drugs.

    Conclusions: In this setting, the indicator sets had high specificity and low sensitivity. This needs to be considered upon use and interpretation.

  • 3707. Wallerstedt, Susanna M.
    et al.
    Fastbom, Johan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Johnell, Kristina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Sjöberg, Christina
    Landahl, Sten
    Sundström, Anders
    Drug Treatment in Older People before and after the Transition to a Multi-Dose Drug Dispensing System-A Longitudinal Analysis2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 6, article id e67088Article in journal (Refereed)
    Abstract [en]

    Background

    An association has been found between multi-dose drug dispensing (MDD) and use of many drugs. The aim of this study was to investigate the nature of this association, by performing a longitudinal analysis of the drug treatment before and after the transition to MDD.

    Methods

    Inclusion critera in this register-based study were inhabitants in Region Vastra Gotaland, Sweden, who, at >= 65 years of age and between 1st July 2006 and 30th June 2010, filled their first MDD prescription. For each individual, prescribed drugs were estimated at three month intervals before and after (maximum 3 years, respectively) the first date of filling an MDD prescription (index date).

    Results

    A total of 30,922 individuals matched the inclusion criteria (mean age: 83.2 years; 59.9% female). There was a temporal association between the transition to MDD and an increased number of drugs: 5.4 +/- 3.9 and 7.5 +/- 3.8 unique drugs three months before and after the index date, respectively, as well as worse outcomes on several indicators of prescribing quality. When either data before or after the index date were used, a multi-level regression analysis predicted the number of drugs at the index date at 5.76 (95% confidence limits: 5.71; 5.80) and 7.15 (7.10; 7.19), respectively, for an average female individual (83.2 years, 10.8 unique diagnoses, 2.4 healthcare contacts/three months). The predicted change in the number of drugs, from three months before the index date to the index date, was greater when data before this date was used as compared with data after this date: 0.12 (0.09; 0.14) versus 0.02 (-0.01; 0.05).

    Conclusions

    After the patients entered the MDD system, they had an increased number of drugs, more often potentially harmful drug treatment, and fewer changes in drug treatment. These findings support a causal relationship between such a system and safety concerns as regards prescribing practices.

  • 3708. Wallerstedt, Susanna M.
    et al.
    Fastbom, Johan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Linke, Johannes
    Vitols, Sigurd
    Long-term use of proton pump inhibitors and prevalence of disease-and drug-related reasons for gastroprotection-a cross-sectional population-based study2017In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 26, no 1, p. 9-16Article in journal (Refereed)
    Abstract [en]

    Purpose To analyse the prevalence of long-term use of proton pump inhibitors (PPI) with respect to underlying diseases and drugs, and to find predictors for such treatment when an evident rationale for the PPI treatment is lacking. Methods The study cohort consisted of individuals, >= 65 years in 2010, residing in the Region Vastra Gotaland during 2005-2010. For individuals with and without long-term use of PPI in 2010, we investigated the prevalence of an underlying diagnosis, that is, an acid-related disease during the five preceding years, as well as concomitant long-term use of antiplatelet agents or cyclooxygenase inhibitors. Results In all, 278 205 individuals (median age: 74 years; 55% female; median 3 drugs per person; 5% nursing home residents, 11% with multi-dose drug dispensing) were included in the analyses, 32 421 (12%) of whom were on long-term treatment with PPI in 2010. For 12 253 individuals (38%) with such treatment, no underlying rationale was found. In individuals without a disease-or a drug-related reason for PPI use, nursing home residence, number of drugs, female sex, but not multi-dose drug dispensing, were associated with long-term use of PPI; adjusted odds ratios (95% confidence interval): 1.63 (1.49; 1.78), 1.27 (1.26; 1.28), 1.24 (1.19; 1.29), and 0.94 (0.88; 1.01), respectively. Conclusions Long-term use of PPI occurs in one out of nine individuals in the older population. For four out of ten of these, no reason for PPI use can be identified. Nursing home residence, female sex, and greater number of drugs predict non-rational long-term use of PPI.

  • 3709. Wallin, Alma Sorberg
    et al.
    Falkstedt, Daniel
    Allebeck, Peter
    Melin, Bo
    Janszky, Imre
    Hemmingsson, Tomas
    Stockholm University, Faculty of Social Sciences, Centre for Social Research on Alcohol and Drugs (SoRAD). Karolinska Institutet, Sweden.
    Does high intelligence improve prognosis?: The association of intelligence with recurrence and mortality among Swedish men with coronary heart disease2015In: Journal of Epidemiology and Community Health, ISSN 0143-005X, E-ISSN 1470-2738, Vol. 69, no 4, p. 347-353Article in journal (Refereed)
    Abstract [en]

    Background Lower intelligence early in life is associated with increased risks for coronary heart disease (CHD) and mortality. Intelligence level might affect compliance to treatment but its prognostic importance in patients with CHD is unknown. Methods A cohort of 1923 Swedish men with a measure of intelligence from mandatory military conscription in 1969-1970 at age 18-20, who were diagnosed with CHD 1991-2007, were followed to the end of 2008. Primary outcome: recurrent CHD event. Secondary outcome: case fatality from the first event, cardiovascular and all-cause mortality. National registers provided information on CHD events, comorbidity, mortality and socioeconomic factors. Results The fully adjusted HRs for recurrent CHD for medium and low intelligence, compared with high intelligence, were 0.98, (95% CIs 0.83 to 1.16) and 1.09 (0.89 to 1.34), respectively. The risks were increased for cardiovascular and all-cause mortality with lower intelligence, but were attenuated in the fully adjusted models (fully adjusted HRs for cardiovascular mortality 1.92 (0.94 to 3.94) and 1.98 (0.89 to 4.37), respectively; for all-cause mortality 1.63 (1.00 to 2.65) and 1.62 (0.94 to 2.78), respectively). There was no increased risk for case-fatality at the first event (fully adjusted ORs 1.06 (0.73 to 1.55) and 0.97 (0.62 to 1.50), respectively). Conclusions Although we found lower intelligence to be associated with increased mortality in middle-aged men with CHD, there was no evidence for its possible effect on recurrence in CHD.

  • 3710.
    Wallin, Cecilia
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Kulkarni, Yashraj S.
    Abelein, Axel
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Karolinska Institutet, Sweden.
    Jarvet, Jüri
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. The National Institute of Chemical Physics and Biophysics, Estonia.
    Liao, Qinghua
    Strodel, Birgit
    Olsson, Lisa
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Luo, Jinghui
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. University of Oxford, UK.
    Abrahams, Jan Pieter
    Sholts, Sabrina B.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. National Museum of Natural History, USA.
    Roos, Per M.
    Kamerlin, Shina C. L.
    Gräslund, Astrid
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Wärmländer, Sebastian K. T. S.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Characterization of Mn(II) ion binding to the amyloid-beta peptide in Alzheimer's disease2016In: Journal of Trace Elements in Medicine and Biology, ISSN 0946-672X, E-ISSN 1878-3252, Vol. 38, p. 183-193Article in journal (Refereed)
    Abstract [en]

    Growing evidence links neurodegenerative diseases to metal exposure. Aberrant metal ion concentrations have been noted in Alzheimer's disease (AD) brains, yet the role of metals in AD pathogenesis remains unresolved. A major factor in AD pathogenesis is considered to be aggregation of and amyloid formation by amyloid-beta (A beta) peptides. Previous studies have shown that A beta displays specific binding to Cu(II) and Zn(II) ions, and such binding has been shown to modulate A beta aggregation. Here, we use nuclear magnetic resonance (NMR) spectroscopy to show that Mn(II) ions also bind to the N-terminal part of the A beta(1-40) peptide, with a weak binding affinity in the milli- to micromolar range. Circular dichroism (CD) spectroscopy, solid state atomic force microscopy (AFM), fluorescence spectroscopy, and molecular modeling suggest that the weak binding of Mn(II) to A beta may not have a large effect on the peptide's aggregation into amyloid fibrils. However, identification of an additional metal ion displaying A beta binding reveals more complex AD metal chemistry than has been previously considered in the literature.

  • 3711.
    Wallin, Erik
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Theoretical studies of Membrane Proteins: Properties, Prediction Methods and Genome-wide analysis1999Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Membrane proteins are a large and important class of proteins. They are responsible for several of the key functions in a living cell, e.g. transport of nutrients and ions, cell-cell signaling, and cell-cell adhesion.

    Despite their importance it has not been possible to study their structure and organization in much detail because of the difficulty to obtain 3D structures.

    In this thesis theoretical studies of membrane protein sequences and structures have been carried out by analyzing existing experimental data. The data comes from several sources including sequence databases, genome sequencing projects, and 3D structures. Prediction of the membrane spanning regions by hydrophobicity analysis is a key technique used in several of the studies. A novel method for this is also presented and compared to other methods.

    The primary questions addressed in the thesis are: What properties are common to all membrane proteins? What is the overall architecture of a membrane protein? What properties govern the integration into the membrane? How many membrane proteins are there and how are they distributed in different organisms? Several of the findings have now been backed up by experiments.

    An analysis of the large family of G-protein coupled receptors pinpoints differences in length and amino acid composition of loops between proteins with and without a signal peptide and also differences between extra- and intracellular loops. Known 3D structures of membrane proteins have been studied in terms of hydrophobicity, distribution of secondary structure and amino acid types, position specific residue variability, and differences between loops and membrane spanning regions.

    An analysis of several fully and partially sequenced genomes from eukaryotes, prokaryotes, and archaea has been carried out. Several differences in the membrane protein content between organisms were found, the most important being the total number of membrane proteins and the distribution of membrane proteins with a given number of transmembrane segments. Of the properties that were found to be similar in all organisms, the most obvious is the bias in the distribution of positive charges between the extra- and intracellular loops.

    Finally, an analysis of homologues to membrane proteins with known topology uncovered two related, multi-spanning proteins with opposite predicted orientations. The predicted topologies were verified experimentally, providing a first example of "divergent topology evolution".

  • 3712.
    Wallin, Karin
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Boström, Gustaf
    Kivipelto, Miia
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Gustafson, Yngve
    Risk factors for incident dementia in the very old2013In: International psychogeriatrics, ISSN 1041-6102, E-ISSN 1741-203X, Vol. 25, no 7, p. 1135-1143Article in journal (Refereed)
    Abstract [en]

    Background: Several risk factors for dementia, Alzheimer's disease, and cognitive impairment have been established; however, knowledge about risk factors in the very old population (>= 85 years) is limited. This study describes the association of several baseline factors with dementia in participants aged >= 85 years, and investigates factors associated with a higher risk of incident dementia over five years. Methods: The participants in this population-based cohort study were aged 85, 90, and >= 95 years at baseline (2000-2002). Data were collected during home visits for interviews and testing, from a review of medical records, and/or interviewing the caregiver or next of kin. After five years 212 participants could be followed up concerning incident dementia. Multivariate logistic regression was used. Results: At baseline, 100/353 (28%) of participants had a dementia diagnosis. Over five years, 71/212 (33.5%) participants developed dementia. Few participants with dementia at baseline remained alive after five years (12%). Depression at the baseline and follow-up time were associated with a higher risk of dementia, odds ratio (OR) (95% CI, p-value) 2.91 (1.37-6.16, 0.005) and 1.61 (1.26-2.05, <0.001) respectively. More social contact and a higher Mini-Mental State Examination score at baseline were associated with lower risk of incident dementia, OR (95% CI, p-value) 0.87 (0.78-0.97, 0.009) and 0.83 (0.74-0.93, 0.001) respectively. Conclusions: Prevalence and incidence of dementia are high in very old people and dementia appears to be a fatal disorder. Depression is associated with higher risk of incident dementia over five years whereas more frequent social contacts and a higher MMSE score are associated with lower risk.

  • 3713.
    Wallin, Karin
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Solomon, Alina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Kåreholt, Ingemar
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Tuomilehto, Jaakko
    Soininen, Hilkka
    Kivipelto, Miia
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Midlife rheumatoid arthritis increases the risk of cognitive impairment two decades later: a population based study2012In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 31, no 3, p. 669-676Article in journal (Refereed)
    Abstract [en]

    Inflammation has been associated with Alzheimer's disease (AD) and dementia. The association between rheumatoid arthritis (RA) or arthritis and dementia/AD has been investigated in several case-control or hospital- and register-based studies with mixed results. This long-term population-based study investigates the association between presence of joint disorders (RA and other joint disorders) in midlife and cognitive status later in life. 1,449 participants were first evaluated in 1972, 1977, 1982, and 1987 and follow-up was performed after 21 years. A self-administered questionnaire including questions on joint disorders was used at both evaluations. Cognitive status (control, mild cognitive impairment, dementia/AD) was assessed at follow-up. The presence of any joint disorder in midlife was significantly associated with a worse cognitive status later in life: OR (95% CI) in an ordinal logistic regression analysis adjusted for age, gender, follow-up time, education, APOE epsilon 4, body mass index, smoking, drug treatment, and diabetes was 1.96 (1.17-3.28). For RA only, OR (95% CI) was 2.77 (1.26-6.10). The correlation remained significant for RA when AD was considered instead of dementia OR (95% CI) 2.49 (1.09-5.67). The presence of joint disorders, especially RA, at midlife seems to be associated with a worse cognitive status later in life. Given the chronic inflammatory component of RA, this study suggests that inflammatory mechanisms may have an important role in increasing the risk of cognitive impairment and dementia/AD.

  • 3714. Wallner, Bengt
    et al.
    Björ, Ove
    Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden; Macquarie University, Australia.
    Hellström, Per M.
    Forsberg, Anna M.
    Talley, Nicholas J.
    Agreus, Lars
    Identifying clinically relevant sliding hiatal hernias: a population-based endoscopy study2018In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 53, no 6, p. 657-660Article in journal (Refereed)
    Abstract [en]

    Objectives: The clinical relevance of small to moderate sliding hiatal hernias is controversial. The aims of the present study were to (1) investigate which symptoms are associated with sliding hiatal hernias and (2) define the length of a sliding hiatal hernia at which gastrointestinal symptoms occur.

    Methods: A study population representative of the general Swedish population answered a questionnaire regarding gastrointestinal symptoms and was investigated with an upper endoscopy. The length of any sliding hiatal hernia was measured.

    Results: Only reflux-related symptoms were associated with length of the hiatal hernia (acid regurgitation OR 1.46, CI 1.19-1.79, heartburn OR 1.27, CI 1.05-1.54), and the association did not become significant until an axial hiatal hernia length of 2 cm.

    Conclusions: Only reflux symptoms could be attributed to sliding hiatal hernias. Hiatal hernias less than 2 cm should be considered clinically insignificant.

  • 3715. Wall-Wieler, Elizabeth
    et al.
    Almquist, Ylva
    Stockholm University, Faculty of Social Sciences, Department of Public Health Sciences.
    Liu, Can
    Stockholm University, Faculty of Social Sciences, Department of Public Health Sciences. Karolinska Institutet, Sweden.
    Vinnerljung, Bo
    Stockholm University, Faculty of Social Sciences, Department of Public Health Sciences. Karolinska Institutet, Sweden.
    Hjern, Anders
    Stockholm University, Faculty of Social Sciences, Department of Public Health Sciences. Karolinska Institutet, Sweden.
    Intergenerational transmission of out-of-home care in Sweden: A population-based cohort study2018In: International Journal of Child Abuse & Neglect, ISSN 0145-2134, E-ISSN 1873-7757, Vol. 83, p. 42-51Article in journal (Refereed)
    Abstract [en]

    The objective of this study is to examine the intergenerational transmission of out-of-home care. This population-based study used data from the Swedish National Registers and included all children born in Sweden between 1990 and 2012 (followed for up to 13 years), whose parents were both born in Sweden between 1973 and 1980 (278 327 children; 145 935 mothers; 146 896 fathers). Cox regression models are used to obtain crude and adjusted hazard ratios (HR) of OHC placement among children based on parents’ history of OHC. Compared with children whose parents both did not have a history of OHC, the risk of being placed in OHC was greater when both parents spent time in OHC (crude HR = 48.70, 95% CI 41.46–57.21; adjusted HR = 3.04, 95% CI = 2.54–3.64), however, children who had only one parent who spent time in care were also at higher risk (mothers only adjusted HR = 2.37, 95% CI = 2.08–2.70; fathers only adjusted HR = 1.33, 95% CI = 1.13–1.55). The crude rate of placement in OHC was highest for children whose parents were placed in care during adolescence, but after adjusting for social and behavioral covariates, children whose parents were in care in early childhood were at greater risk of OHC than children whose parents were in care in adolescence. To reduce this intergenerational transmission of OHC, more supports should be provided to parents who spent time in OHC to ensure a successful transition to parenthood.

  • 3716. Wall-Wieler, Elizabeth
    et al.
    Bolton, James
    Liu, Can
    Stockholm University, Faculty of Social Sciences, Department of Public Health Sciences. Karolinska Institutet, Sweden.
    Wilcox, Holly
    Roos, Leslie L.
    Hjern, Anders
    Stockholm University, Faculty of Social Sciences, Department of Public Health Sciences. Karolinska Institutet, Sweden.
    Intergenerational involvement in out-of-home care and death by suicide in Sweden: A population-based cohort study2018In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 238, p. 506-512Article in journal (Refereed)
    Abstract [en]

    Background: Individuals involved in out-of-home care are at higher risk of death by suicide. We aimed to determine whether parents with two generations of involvement in out-of-home care (themselves as children, and their own children) are at increased risk of death by suicide than parents with no involvement or parents with one generation of involvement in out-of-home care. Method: This population-based cohort study included all individuals born in Sweden between 1973 and 1980 who had at least one child between 1990 and 2012 (n=487,948). Women (n=259,275) and men (n=228,673) were examined separately. Results: When compared with mothers with no involvement in out-of-home care, mothers with two generations of involvement were at more than five times greater risk of death by suicide (aHR=5.52; 95% CI 2.91-10.46); mothers with one generation of involvement were also at significantly higher risk of death by suicide (mothers were in care as children: aHR=2.35; 95% CI 1.27-4.35; child was placed in care: aHR=3.23; 95% CI 1.79-5.83). Involvement in out-of-home care (in either generation) did not affect risk of death by suicide for fathers. Limitations: Reason for placement in out-of-home care is not known; these reasons could also be associated with risk of death by suicide Conclusion: Mothers with involvement in out- of-home care, either as children or when their child was placed in care, are at significantly higher risk of death by suicide. Mental health services should be provided to individuals involved in out-of-home care.

  • 3717.
    Wallén, Martin Benka
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Hasson, Dan
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Theorell, Töres
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Canlon, Barbara
    Osika, Walter
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Possibilities and limitations of the polar RS800 in measuring heart rate variability at rest2012In: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 112, no 3, p. 1153-1165Article in journal (Refereed)
    Abstract [en]

    A growing trend among clinical studies is the use of heart rate monitors (HRMs) for assessment of heart rate variability (HRV). These instruments offer a convenient alternative to traditional electrocardiographs (ECGs) for recording and processing of R-R data. Reports on the validity of such systems are, however, conflicting. This study aimed to assess the validity of a commercial HRM on a large study sample, with emphasis on gender and age. Simultaneous recordings of R-R intervals were conducted with the Polar RS800 HRM and a 3-lead ECG on 341 individuals. Data editing was performed with individually designated software for each instrument. Agreement on SDNN, RMSSD, and HF- and LF power was assessed with intraclass correlations (ICCs), standard errors of measurement (SEMs) and Bland and Altman plots. The HRM was not able to identify 18 observations with non-sinus beats. For men, agreement between instruments ranged from good to excellent (ICC >= 0.8) on all HRV measures, and SEMs were generally small. For women the results were weaker, with unacceptable agreement between instruments on SDNN. Women over 60 years did not reach a critical ICC value of 0.75 on any of the HRV measures. Bland and Altman plots demonstrated that the RS800 generally overestimated HRV, and that uncertainty increased with higher values. Since the Polar system did not identify errors satisfactorily, or return valid values of HRV for certain groups, it is concluded that, whenever possible, traditional ECGs should be used for both gathering and editing of HRV data.

  • 3718. Walter, S. A.
    et al.
    Jones, M. P.
    Talley, N. J.
    Kjellström, L.
    Nyhlin, H.
    Andreasson, Anna N.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institute.
    Agreus, L.
    Abdominal pain is associated with anxiety and depression scores in a sample of the general adult population with no signs of organic gastrointestinal disease2013In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 25, no 9, p. 741-E576Article in journal (Refereed)
    Abstract [en]

    Background Abdominal pain is common in the community, but only a subset meet diagnostic criteria for irritable bowel syndrome (IBS). Although anxiety and depression have been linked to IBS, the role of mood disturbances in the remainder with symptoms remains unclear. We aimed to study the associations between abdominal pain, anxiety, depression, and quality of life in the general population who were free of organic colonic disease by colonoscopy. Methods Two hundred and seventy-two randomly selected subjects from the general population, mean age 54 years (27-71), were clinically evaluated, had a colonoscopy and laboratory investigations to exclude organic gastrointestinal (GI) disease. All subjects completed GI symptom diaries for 1 week, the Rome II modular questionnaire, the Hospital Anxiety and Depression Scale, and Short Form 36. Key Results Twenty-two subjects were excluded due to organic disease; 1532 daily symptom records were available for analysis in the remainder. Thirty-four percent (n = 83) recorded at least one episode of abdominal pain on the diary. Twelve percent fulfilled Rome II criteria for IBS. Both anxiety and depression scores were higher in subjects who reported abdominal pain vs those who did not (P < 0.0005 and P < 0.0005). Anxiety and depression scores independently from IBS diagnosis (Rome II) predicted pain reporting and also correlated positively with pain burden. Quality of life scores were generally lower in subjects with abdominal pain. Conclusions & Inferences Anxiety and depression are linked to functional abdominal pain, not only in subjects with IBS but also in otherwise healthy people with milder, subtle GI symptoms.

  • 3719.
    Waluk, Dominik P.
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Battistini, Matthew R.
    Dempsey, Daniel R.
    Farrell, Emma K.
    Jeffries, Kristen A.
    Mitchell, Perry
    Hernandez, Lucas W.
    McBride, Joshua C.
    Merkler, David J.
    Hunt, Mary C.
    Mammalian Fatty Acid Amides of the Brain and CNS2014In: Omega-3 Fatty Acids in Brain and Neurological Health / [ed] Watson, R. R.; De Meester, F., London: Academic Press Ltd-Elsevier Science Ltd , 2014, p. 87-107Chapter in book (Refereed)
  • 3720.
    Wanderoy, Maria
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Up-regulation of dopamine D₂ receptors: in vitro and in vivo studies1998Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In the central nervous system (CNS) dopaminergic and dopaminoceptive neurons have the ability to respond to variations in dopamine levels by for example adjusting their dopamine receptor levels. One of the most well known phenomena in this respect is that long-term blockade of D2 receptors with antipsychotic drugs leads to an increase in striatal D2 receptor density of experimental animals as well as of schizophrenic patients as measured in both post-mortem studies and in vivo positron emission tomography studies of brain. Whether such a response underlies schizophrenic symptoms, is an effect of drug treatment, or both has yet to be clarified.

    Knowledge of underlying molecular mechanisms of D2 receptor up-regulation is sparse due to the difficulty in examining such effects both in vivo and in vitro. This work mainly describes a way to overcome these obstacles by: (1) presenting a cellular system where increased D2 receptor levels and a supersensitive D2 coupled functional response can be evoked by persistent "indirect" blockade of the receptor (2) identifying some of the molecular aspects underlying this up-regulation and (3) validating parts of this cellular model in vivo in the rat striatum.

    By persistently stimulating the adenylyl cyclase enzyme with forskolin in mouse Ltk- fibroblast cells stably transfected with the human long D2 receptor (D2L) (and thereby mimicking long-term D2 receptor block at the level of intracellular cAMP), D2 receptors could be up-regulated by 43%. A supersensitive response to dopamine was found in parallel. The increase in receptor number was even larger (105%) for the short D2 receptor variant. The forskolin-induced up-regulation of D2L receptors was found to be dependent on: (1) increases in intracellular cAMP levels (2) de novo protein synthesis (3) activation of protein kinase A (PKA) and (4) at least partially on an intact Gi/o protein pool. Forskolin infusion into rat lateral ventricles produced D2 receptor increases of 19% and D1 receptor decreases of 27%. In vivo effects in the rats following the forskolin infusion, most likely a function of the D2 receptor up-regulation, were shown in both behavioral and biochemical experiments. The relevance of studying D2 receptor up-regulation was strengthened by findings where subchronic treatment of rats with the atypical antipsychotic remoxipride resulted in D2 receptor up-regulation in brain regions that have receptor levels that are 38-fold lower than in the striatum. Parallel control treatments with the typical antipsychotic haloperidol gave similar results.

    In conclusion, the work presents an in vitro possibility for studying molecular mechanisms of D2 receptor up-regulation. The cellular model has been characterized in several respects and partly validated in an in vivo system. There seems to be good reason to pursue these issues further as the new generation of atypical antipsychotics are also likely to target and affect D2 receptor numbers in the brain.

  • 3721. Wang, Chao
    et al.
    Klechikov, Alexey G.
    Gharibyan, Anna L.
    Wärmländer, Sebastian K. T. S.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Jarvet, Jüri
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. National Institute of Chemical Physics & Biophysics (NICPB), Estonia.
    Zhao, Lina
    Jia, Xueen
    Shankar, S. K.
    Olofsson, Anders
    Brännström, Thomas
    Mu, Yuguang
    Gräslund, Astrid
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Morozova-Roche, Ludmilla A.
    The role of pro-inflammatory S100A9 in Alzheimer's disease amyloid-neuroinflammatory cascade2014In: Acta Neuropathologica, ISSN 0001-6322, E-ISSN 1432-0533, Vol. 127, no 4, p. 507-522Article in journal (Refereed)
    Abstract [en]

    Pro-inflammatory S100A9 protein is increasingly recognized as an important contributor to inflammation-related neurodegeneration. Here, we provide insights into S100A9 specific mechanisms of action in Alzheimer's disease (AD). Due to its inherent amyloidogenicity S100A9 contributes to amyloid plaque formation together with A beta. In traumatic brain injury (TBI) S100A9 itself rapidly forms amyloid plaques, which were reactive with oligomer-specific antibodies, but not with A beta and amyloid fibrillar antibodies. They may serve as precursor-plaques for AD, implicating TBI as an AD risk factor. S100A9 was observed in some hippocampal and cortical neurons in TBI, AD and non-demented aging. In vitro S100A9 forms neurotoxic linear and annular amyloids resembling A beta protofilaments. S100A9 amyloid cytotoxicity and native S100A9 pro-inflammatory signaling can be mitigated by its co-aggregation with A beta, which results in a variety of micron-scale amyloid complexes. NMR and molecular docking demonstrated transient interactions between native S100A9 and A beta. Thus, abundantly present in AD brain pro-inflammatory S100A9, possessing also intrinsic amyloidogenic properties and ability to modulate A beta aggregation, can serve as a link between the AD amyloid and neuroinflammatory cascades and as a prospective therapeutic target.

  • 3722.
    Wang, He
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Metabolic regulation of nitrogen fixation in Rhodospirillum rubrum2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Nitrogen, along with carbon, hydrogen and oxygen, is amongst the most abundant elements in all living cells. The capability to convert atmospheric dinitrogen to biologically usable nitrogen compounds is only found in some prokaryotes. Biological nitrogen fixation, the reduction of dinitrogen to ammonia, is the entry step into the global nitrogen cycle. Nitrogenase, the enzyme responsible for dinitrogen reduction, requires large amounts of ATP and reducing equivalents. Consequently, the nitrogen fixation process is subjected to sophisticated regulatory networks that respond to multiple environmental stimuli. In the free-living photosynthetic nitrogen-fixing bacterium Rhodospirillum rubrum, the activity of nitrogenase is tightly regulated at the post-translational level by reversible ADP-ribosylation in response to cellular changes in nitrogen and energy status, the so-called “switch-off” effect. Our studies have been focused on identifying the intracellular signal(s) and protein components acting during “switch-off”, and elucidating the mechanism underlying this regulation. We have shown that PII signal transduction proteins and the ammonium transporter AmtB1 play central roles in the signal transduction pathway leading to the post-translational regulation of nitrogenase, in particular, the involvement of AmtB1-PII complex formation during ammonium “switch-off”. In contrast, a different signaling pathway is operating during the energy “switch-off”, and several interesting differences are highlighted here. In addition, we have solved a high-resolution structure of Dinitrogenase Reductase Activating Glycohydrolase (DRAG) using X-ray crystallography. A detailed mechanism of ADP-ribose removal by DRAG is proposed, with our structural and functional studies on DRAG supporting a reversible membrane association mechanism of regulating its activity, further controlling the activity of nitrogenase.

  • 3723.
    Wang, Hui-Xin
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Gustafson, Deborah R
    Kivipelto, Miia
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Pedersen, Nancy L
    Skoog, Ingmar
    Windblad, Bengt
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Education halves the risk of dementia due to apolipoprotein ε4 allele: a collaborative study from the Swedish brain power initiative2012In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 33, no 5, p. 1007.e1-1007.e7Article in journal (Refereed)
    Abstract [en]

    A number of studies have explored the relationships of apolipoprotein E (APOE) genotype and education with dementia over the last decade. However, observations concerning the possible modifying effect of education on the APOE-dementia association are limited. The objective of this study was to test the hypothesis that education may decrease the risk of APOE ε4 on dementia. Pooled data from 3 major population-based studies in Northern Europe were used in this study, with a total of 3436 participants aged 65 and older derived from the Kungsholmen project and the Gothenburg Birth Cohort studies in Sweden, and the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) project in Finland. The main outcome measure was dementia, which was diagnosed in 219 persons according to standard criteria. APOE ε4 was associated with increased risk of dementia independent of the effect of education (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.9-3.4 for 1 ε4 carrier and OR, 3.7; 95% CI, 1.8-7.2 for 2 ε4 carriers). High education (8 years and more) was related to a lower dementia risk (OR, 0.5; 95% CI, 0.3-0.6). An interaction between education and APOE ε4 was observed. Compared with those with less education and no ε4, the odds of dementia among persons with low education who carried any ε4 allele was 2.7 (95% CI, 1.9-3.9), and 1.2 (0.7-1.8) if they had higher education. This study suggests that genetic (APOE ε4) and environmental (education) factors are not only independently but also interactively related to dementia risk and that high education may buffer the negative effect of APOE ε4 on dementia occurrence.

  • 3724.
    Wang, Hui-Xin
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Jin, Yinlong
    Hendrie, Hugh C.
    Liang, Chaoke
    Yang, Lili
    Cheng, Yibin
    Unverzagt, Frederick W.
    Ma, Feng
    Hall, Kathleen S.
    Murrell, Jill R.
    Li, Ping
    Bian, Jianchao
    Pei, Jin-Jing
    Gao, Sujuan
    Late Life Leisure Activities and Risk of Cognitive Decline2013In: The journals of gerontology. Series A, Biological sciences and medical sciences, ISSN 1079-5006, E-ISSN 1758-535X, Vol. 68, no 2, p. 205-213Article in journal (Refereed)
    Abstract [en]

    Background. Studies concerning the effect of different types of leisure activities on various cognitive domains are limited. This study tests the hypothesis that mental, physical, and social activities have a domain-specific protection against cognitive decline. Methods. A cohort of a geographically defined population in China was examined in 2003-2005 and followed for an average of 2.4 years. Leisure activities were assessed in 1,463 adults aged 65 years and older without cognitive or physical impairment at baseline, and their cognitive performances were tested at baseline and follow-up examinations. Results. High level of mental activity was related to less decline in global cognition (beta = -.23, p < .01), language (beta = -.11, p < .05), and executive function (beta = -.13, p < .05) in ANCOVA models adjusting for age, gender, education, history of stroke, body mass index, Apolipoprotein E genotype, and baseline cognition. High level of physical activity was related to less decline in episodic memory (beta = -.08, p < .05) and language (beta = -.15, p < .01). High level of social activity was associated with less decline in global cognition (beta = -.11, p < .05). Further, a dose-response pattern was observed: although participants who did not engage in any of the three activities experienced a significant global cognitive decline, those who engaged in any one of the activities maintained their cognition, and those who engaged in two or three activities improved their cognition. The same pattern was observed in men and in women. Conclusions. Leisure activities in old age may protect against cognitive decline for both women and men, and different types of activities seem to benefit different cognitive domains.

  • 3725.
    Wang, Hui-Xin
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Kivipelto, Miia
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Dementia2012In: HANDBOOK OF CLINICAL GENDER MEDICINE / [ed] SchenckGustafsson, K; DeCola, PR; Pfaff, DW; Pisetsky, DS, Basel: Karger , 2012, p. 495-503Chapter in book (Refereed)
    Abstract [en]

    Dementia is the most common mental disorder contributing greatly to disability, institutionalization, and shorter survival among the older population of both genders. Both the prevalence and incidence of dementia are higher in women than in men after the age of 80. Men and women have different profiles concerning risk factors and outcomes of dementia, with most of them favoring men. Epidemiological and experimental studies have indicated that estrogen would protect against dementia and Alzheimer's disease. However, evidence is still lacking that hormonal replacement therapy could protect against dementia. The role of male sex hormones for dementia risk has been less investigated. Although the causes of gender differences remain poorly understood, awareness of these differences may help identify persons at risk for dementia, affect its prognosis, and have implications for disease prevention.

  • 3726.
    Wang, Hui-Xin
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Zhengzhou University, China.
    MacDonald, Stuart W S
    Dekhtyar, Serhiy
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm Gerontology Research Center, Sweden.
    Association of lifelong exposure to cognitive reserve-enhancing factors with dementia risk: A community-based cohort study2017In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 14, no 3, article id e1002251Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Variation in the clinical manifestation of dementia has been associated with differences in cognitive reserve, although less is known about the cumulative effects of exposure to cognitive reserve factors over the life course. We examined the association of cognitive reserve-related factors over the lifespan with the risk of dementia in a community-based cohort of older adults.

    METHODS AND FINDINGS: Information on early-life education, socioeconomic status, work complexity at age 20, midlife occupation attainment, and late-life leisure activities was collected in a cohort of dementia-free community dwellers aged 75+ y residing in the Kungsholmen district of Stockholm, Sweden, in 1987-1989. The cohort was followed up to 9 y (until 1996) to detect incident dementia cases. To exclude preclinical phases of disease, participants who developed dementia at the first follow-up examination 3 y after the baseline were excluded (n = 602 after exclusions). Structural equation modelling was used to generate latent factors of cognitive reserve from three periods over the life course: early (before 20 y), adulthood (around 30-55 y), and late life (75 y and older). The correlation between early- and adult-life latent factors was strong (γ = 0.9), whereas early-late (γ = 0.27) and adult-late (γ = 0.16) latent factor correlations were weak. One hundred forty-eight participants developed dementia during follow-up, and 454 remained dementia-free. The relative risk (RR) of dementia was estimated using Cox models with life-course cognitive reserve-enhancing factors modelled separately and simultaneously to assess direct and indirect effects. The analysis was repeated among carriers and noncarriers of the apolipoprotein E (APOE) ε4 allele. A reduced risk of dementia was associated with early- (RR 0.57; 95% CI 0.36-0.90), adult- (RR 0.60; 95% CI 0.42-0.87), and late-life (RR 0.52; 95% CI 0.37-0.73) reserve-enhancing latent factors in separate multivariable Cox models. In a mutually adjusted model, which may have been imprecisely estimated because of strong correlation between early- and adult-life factors, the late-life factor preserved its association (RR 0.65; 95% CI 0.45-0.94), whereas the effect of midlife (RR 0.73; 95% CI 0.50-1.06) and early-life factors (RR 0.76; 95% CI 0.47-1.23) on the risk of dementia was attenuated. The risk declined progressively with cumulative exposure to reserve-enhancing latent factors, and having high scores on cognitive reserve-enhancing composite factors in all three periods over the life course was associated with the lowest risk of dementia (RR 0.40; 95% CI 0.20-0.81). Similar associations were detected among APOE ε4 allele carriers and noncarriers. Limitations include measurement error and nonresponse, with both biases likely favouring the null. Strong correlation between early- and adult-life latent factors may have led to a loss in precision when estimating mutually adjusted effects of all periods.

    CONCLUSIONS: In this study, cumulative exposure to reserve-enhancing factors over the lifespan was associated with reduced risk of dementia in late life, even among individuals with genetic predisposition.

  • 3727.
    Wang, Hui-Xin
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Wahlberg, Maria
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Karp, Anita
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Winblad, Bengt
    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).
    Psychosocial stress at work is associated with increased dementia risk in late life2012In: ALZHEIMERS & DEMENTIA, ISSN 1552-5260, Vol. 8, no 2, p. 114-120Article in journal (Refereed)
    Abstract [en]

    Objective: To test the hypothesis that high job stress during working life might lead to an increased risk of dementia and Alzheimer's disease (AD) in late life. Methods: A dementia-free cohort of 913 community dwellers, aged 75+ years, from the Kungsholmen Project, a population-based follow-up study carried out in Stockholm, Sweden, was followed up for an average of 6 years to detect incident dementia and AD (third revised Diagnostic and Statistical Manual of Mental Disorders). Information on the lifespan work activities was collected. Psychological stress at work was estimated for the longest period of occupation as well as for all occupations by using a validated psychosocial job exposure matrix on two dimensions: job control and job demands. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of dementia and AD in relation to different levels of job stress. Results: Low level of job control was associated with higher multivariate adjusted risk of dementia (HR = 1.9, 95% CI: 1.2-3.0) and AD (HR = 2.2, 95% CI: 1.2-3.9). Low level of job demands alone was not significantly associated with increased dementia risk. When the two dimensions were combined into a four-category job strain model, both high job strain (low control/high demands) and passive strain (both low control and demands) were related to higher risk of dementia and AD as compared with active job strain (both high). Vascular disorders did not mediate the observed associations. Conclusion: Lifelong work-related psychosocial stress, characterized by low job control and high job strain, was associated with increased risk of dementia and AD in late life, independent of other known risk factors.

  • 3728. Wang, Meng
    et al.
    Beelen, Rob
    Stafoggia, Massimo
    Raaschou-Nielsen, Ole
    Andersen, Zorana Jovanovic
    Hoffmann, Barbara
    Fischer, Paul
    Houthuijs, Danny
    Nieuwenhuijsen, Mark
    Weinmayr, Gudrun
    Vineis, Paolo
    Xun, Wei W.
    Dimakopoulou, Konstantina
    Samoli, Evangelia
    Laatikainen, Tiina
    Lanki, Timo
    Turunen, Anu W.
    Oftedal, Bente
    Schwarze, Per
    Aamodt, Geir
    Penell, Johanna
    De Faire, Ulf
    Korek, Michal
    Leander, Karin
    Pershagen, Göran
    Pedersen, Nancy L.
    Östenson, Claes-Göran
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Thorup Eriksen, Kirsten
    Sörensen, Mette
    Tjönneland, Anne
    Bueno-de-Mesquita, Bas
    Eeftens, Marloes
    Bots, Michiel L.
    Meliefste, Kees
    Kraemer, Ursula
    Heinrich, Joachim
    Sugiri, Dorothea
    Key, Timothy
    de Hoogh, Kees
    Wolf, Kathrin
    Peters, Annette
    Cyrys, Josef
    Jaensch, Andrea
    Concin, Hans
    Nagel, Gabriele
    Tsai, Ming-Yi
    Phuleria, Harish
    Ineichen, Alex
    Kuenzli, Nino
    Probst-Hensch, Nicole
    Schaffner, Emmanuel
    Vilier, Alice
    Clavel-Chapelon, Francoise
    Declerq, Christophe
    Ricceri, Fulvio
    Sacerdote, Carlotta
    Marcon, Alessandro
    Galassi, Claudia
    Migliore, Enrica
    Ranzi, Andrea
    Cesaroni, Giulia
    Badaloni, Chiara
    Forastiere, Francesco
    Katsoulis, Michail
    Trichopoulou, Antonia
    Keuken, Menno
    Jedynska, Aleksandra
    Kooter, Ingeborg M.
    Kukkonen, Jaakko
    Sokhi, Ranjeet S.
    Brunekreef, Bert
    Katsouyanni, Klea
    Hoek, Gerard
    Long-term exposure to elemental constituents of particulate matter and cardiovascular mortality in 19 European cohorts: Results from the ESCAPE and TRANSPHORM projects2014In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 66, p. 97-106Article in journal (Refereed)
    Abstract [en]

    Background: Associations between long-term exposure to ambient particulate matter (PM) and cardiovascular (CVD) mortality have been widely recognized. However, health effects of long-term exposure to constituents of PM on total CVD mortality have been explored in a single study only. Aims: The aim of this study was to examine the association of PM composition with cardiovascular mortality. Methods: We used data from 19 European ongoing cohorts within the framework of the ESCAPE (European Study of Cohorts for Air Pollution Effects) and TRANSPHORM (Transport related Air Pollution and Health impacts Integrated Methodologies for Assessing Particulate Matter) projects. Residential annual average exposure to elemental constituents within particle matter smaller than 2.5 and 10 pm (PM2.5 and PM10) was estimated using Land Use Regression models. Eight elements representing major sources were selected a priori (copper, iron, potassium, nickel, sulfur, silicon, vanadium and zinc). Cohort-specific analyses were conducted using Cox proportional hazards models with a standardized protocol. Random-effects metaanalysis was used to calculate combined effect estimates. Results: The total population consisted of 322,291 participants, with 9545 CVD deaths. We found no statistically significant associations between any of the elemental constituents in PM2.5 or PM10 and CVD mortality in the pooled analysis. Most of the hazard ratios (HRs) were close to unity, e.g. for PM10 Fe the combined HR was 0.96 (0.84-1.09). Elevated combined HRs were found for PM2.5 Si (1.17, 95% Cl: 0.93-1.47), and S in PM2.5 (1.08,95% Cl: 0.95-1.22) and PM10 (1.09,95% Cl: 0.90-132). Conclusion: In a joint analysis of 19 European cohorts, we found no statistically significant association between long-term exposure to 8 elemental constituents of particles and total cardiovascular mortality.

  • 3729. Wang, Mo
    et al.
    Alexanderson, Kristina
    Runeson, Bo
    Head, Jenny
    Melchior, Maria
    Perski, Aleksander
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Mittendorfer-Rutz, Ellenor
    Are all-cause and diagnosis-specific sickness absence, and sick-leave duration risk indicators for suicidal behaviour? A nationwide register-based cohort study of 4.9 million inhabitants of Sweden2014In: Occupational and Environmental Medicine, ISSN 1351-0711, E-ISSN 1470-7926, Vol. 71, no 1, p. 12-20Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Recent studies have found an increased risk of suicide in people on sickness absence, but less is known about to what extent diagnosis-specific sickness absence is a risk indicator for suicidal behaviour. This study aimed to examine all-cause and diagnosis-specific sickness absence and sick-leave duration as risk indicators for suicide attempt and suicide.

    METHODS: This is a population-based prospective cohort study. All non-retired adults (n=4 923 404) who lived in Sweden as on 31 December 2004 were followed-up for 6 years regarding suicide attempt and suicide (2005-2010). HRs and 95% CIs for suicidal behaviour were calculated, using people with no sick-leave spells in 2005 as reference.

    RESULTS: In analyses adjusted for sociodemographic factors and previous mental healthcare, suicide attempt and current antidepressants prescription, sickness absence predicted suicide attempt (HR 2.37; 95% CI 2.25 to 2.50 for women; HR 2.69; 95% CI 2.53 to 2.86 for men) and suicide (HR 1.91; 95% CI 1.60 to 2.29 for women; HR 1.92; 95% CI 1.71 to 2.14 for men), particularly mental sickness absence (range of HR: 2.74-3.64). The risks were also increased for somatic sickness absence, for example, musculoskeletal and digestive diseases and injury/poisoning (range of HR: 1.57-3.77). Moreover, the risks increased with sick-leave duration.

    CONCLUSIONS: Sickness absence was a clear risk indicator for suicidal behaviour, irrespective of sick-leave diagnoses, among women and men. Awareness of such risks is recommended when monitoring sickness certification. Further studies are warranted in order to gain more detailed knowledge on these associations.

  • 3730.
    Wang, R.
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Fratiglioni, L.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Laveskog, A.
    Kalpouzos, G.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Ehrenkrona, C. -H
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Zhang, Y.
    Bronge, L.
    Wahlund, L. -O
    Bäckman, L.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Qiu, C.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Do cardiovascular risk factors explain the link between white matter hyperintensities and brain volumes in old age?: A population-based study2014In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 21, no 8, p. 1076-1082Article in journal (Refereed)
    Abstract [en]

    Background and purpose: White matter hyperintensities (WMHs) and brain atrophy frequently coexist in older people. However, it is unclear whether the association between these two brain lesions is dependent on the aging process, a vascular mechanism or genetic susceptibility. It was therefore investigated whether the association between load of WMHs and brain atrophy measures is related to age, vascular risk factors (VRFs) or the APOE-epsilon 4 allele. Methods: This population-based study included 492 participants (age >= 60 years, 59.6% women) free of dementia and stroke. Data on demographics, VRFs and APOE genotypes were collected through interviews, clinical examination and laboratory tests. WMHs on magnetic resonance images were assessed using manual visual rating and automatic volumetric segmentation. Hippocampal and ventricular volumes were manually delineated, whereas total gray matter (GM) volume was measured by automatic segmentation. Data were analyzed with multivariate linear regression models. Results: More global WMHs, assessed using either a visual rating scale or a volumetric approach, were significantly associated with lower GM volume and higher ventricular volume; the associations remained significant after adjusting for age, VRFs and the APOE-epsilon 4 allele. In contrast, the association between global WMHs and hippocampal volume was no longer significant after adjusting for age, whereas adjustment for VRFs and APOE-epsilon 4 had no influential effect. Conclusion: The association of global WMHs with lower GM volume and higher ventricular volume is independent of age, VRFs and APOE-epsilon 4 allele, suggesting that the process of cerebral microvascular disease and neurodegeneration are associated independently of the normal aging process, vascular mechanisms or genetic susceptibility.

  • 3731.
    Wang, Rui
    et al.
    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.
    Kalpouzos, Gregoria
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Lövdén, Martin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Laukka, Erika J.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Bronge, Lena
    Wahlund, Lars-Olof
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm Gerontology Research Center, Sweden.
    Qiu, Chengxuan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Mixed brain lesions mediate the association between cardiovascular risk burden and cognitive decline in old age: A population-based study2017In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 13, no 3, p. 247-256Article in journal (Refereed)
    Abstract [en]

    Introduction: The underlying pathological mechanisms linking cardiovascular burden to cognitive decline remain unclear. Methods: We investigated the associations of the Framingham general cardiovascular risk score (FGCRS), apolipoprotein E (APOE) 64, and brain structure with the Mini-Mental State Examination (MMSE) decline using the 9-year follow-up data from Swedish National Study on Aging and Care in Kungsholmen (n = 2189, age >= 60) and the embedded magnetic resonance imaging (MRI) (n = 448) studies. Volumes of white matter hyperintensities (WMHs), total gray matter, ventricles, and hippo campus were assessed in the MRI sample. Results: A higher FGCRS was associated with faster MMSE decline in young-old people (60-72 years) but not in old-old (>= 78 years). Larger volumes of cerebral WMHs and ventricles and smaller volumes of total gray matter and hippocampus were all associated with accelerated MMSE decline (P <.01); these associations were stronger among APOE epsilon 4 carriers than noncarriers. Simultaneously entering multiple brain lesion markers as mediators in the model substantially attenuated the association between FGCRS and MMSE decline. Discussion: The effect of cardiovascular risk burden on cognitive deterioration in old age is largely mediated by mixed brain lesions.

  • 3732.
    Wang, Rui
    et al.
    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).
    Laukka, Erika J.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Lovden, Martin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Kalpouzos, Gregoria
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Keller, Lina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Graff, Caroline
    Salami, Alireza
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Backman, 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).
    Effects of vascular risk factors and APOE epsilon 4 on white matter integrity and cognitive decline2015In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 84, no 11, p. 1128-1135Article in journal (Refereed)
    Abstract [en]

    Objective:To investigate the effects of vascular risk factors and APOE status on white matter microstructure, and subsequent cognitive decline among older people.Methods:This study included 241 participants (age 60 years and older) from the population-based Swedish National Study on Aging and Care in Kungsholmen in central Stockholm, Sweden, who were free of dementia and stroke at baseline (2001-2004). We collected data through interviews, clinical examinations, and laboratory tests. We measured fractional anisotropy (FA) and mean diffusivity (MD) on diffusion tensor imaging, and estimated volume of white matter hyperintensities using automatic segmentation. We assessed global cognitive function with the Mini-Mental State Examination at baseline and at 3- and/or 6-year follow-up. We analyzed the data using multivariate linear regression and linear mixed models.Results:Heavy alcohol consumption, hypertension, and diabetes were significantly associated with lower FA or higher MD (p < 0.05). When aggregating heavy alcohol consumption, hypertension, and diabetes together with current smoking, having an increasing number of these 4 factors concurrently was associated with decreasing FA and increasing MD (p(trend) < 0.01), independent of white matter hyperintensities. Vascular risk factors and APOE epsilon 4 allele interacted to negatively affect white matter microstructure; having multiple (2) vascular factors was particularly detrimental to white matter integrity among APOE epsilon 4 carriers. Lower tertile of FA and upper tertile of MD were significantly associated with faster Mini-Mental State Examination decline.Conclusions:Vascular risk factors are associated with reduced white matter integrity among older adults, which subsequently predicted faster cognitive decline. The detrimental effects of vascular risk factors on white matter microstructure were exacerbated among APOE epsilon 4 carriers.

  • 3733.
    Wang, Rui
    et al.
    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).
    Liang, Yajun
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Welmer, Anna-Karin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Xu, Weili
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Mangialasche, Francesca
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Johnell, Kristina
    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).
    Prevalence, Pharmacological Treatment, and Control of Cardiometabolic Risk Factors among Older People in Central Stockholm: A Population-Based Study2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 3Article in journal (Refereed)
    Abstract [en]

    Background Cardiometabolic risk factors and related cardiovascular diseases represent major threats to healthy aging. Objective We aimed to estimate distribution, pharmacological treatment, and control of main cardiometabolic risk factors among older people. Methods This population-based study included 3363 participants (age >= 60 years, 64.9% women) in the Swedish National study on Aging and Care in Kungsholmen, in central Stockholm, Sweden (2001-2004). Data on demographics, cardiometabolic risk factors (hypertension, obesity, diabetes, and high cholesterol), and medication use were collected through face-to-face interviews, clinical examinations, laboratory tests, and the inpatient register. Cardiometabolic risk factors were defined following the most commonly used criteria. Prevalence was standardized using local census data. Results The age-and sex-standardized prevalence of diabetes, obesity, high cholesterol, and hypertension was 9.5%, 12.8%, 49.7%, and 74.9%, respectively. The prevalence of hypertension and diabetes increased with age, whereas the prevalence of obesity and high cholesterol decreased with age. Forty-nine percent of older adults had two or more cardiometabolic risk factors; 9.8% had three or more. Overall, 55.5% of people with hypertension, 50.3% with diabetes, and 25.0% with high cholesterol received pharmacological treatment. Of those treated pharmacologically, 49.4%, 38.1%, and 85.5% reached therapeutic goals for hypertension (blood pressure<150/90 mmHg), diabetes (glycated haemoglobin<7%), and high cholesterol (total cholesterol<6.22 mmol/l), respectively. Conclusions Hypertension, high cholesterol, and clustering of cardiometabolic risk factors were common among older people in Stockholm, but pharmacological treatment and control of these major factors can be improved. Appropriate management of cardiometabolic profiles among older people may help improve cardiovascular health and achieve healthy aging.

  • 3734.
    Wang, Rui
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Yan, Zhongrui
    Liang, Yajun
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Jining Medical University, Shandong, China.
    Tan, Edwin C. K.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Monash University, Australia.
    Cai, Chuanzhu
    Jiang, Hui
    Song, Aiqin
    Qiu, Chengxuan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Prevalence and Patterns of Chronic Disease Pairs and Multimorbidity among Older Chinese Adults Living in a Rural Area2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 9Article in journal (Refereed)
    Abstract [en]

    Background The burden of chronic diseases in China is substantial now. Data on patterns of chronic diseases and multimorbidity among older adults, especially among those living in rural areas, are sparse. Objective We aim to investigate the prevalence and patterns of chronic disease pairs and multimorbidity in elderly people living in rural China. Methods This population-based study included 1480 adults aged 60 years and over (mean age 68.5 years, 59.4% women) living in a rural community. Data were derived from the Confucius Hometown Aging Project in Shandong, China (June 2010-July 2011). Chronic diseases were diagnosed through face-to-face interviews, clinical examinations, and laboratory tests. Patterns of chronic disease pairs and multimorbidity were explored using logistic regression and exploratory factor analyses. Results The prevalence of individual chronic diseases ranged from 3.0% for tumor to 76.4% for hypertension, and each disease was often accompanied with three or more other chronic diseases. The observed prevalence of pairs of chronic conditions exceeded the expected prevalence for several conditions, such as cardiovascular diseases and metabolic disorders, as well as pulmonary diseases and degenerative disorders. Chronic multimorbidity (>= 2 chronic diseases) affected more than 90% of subjects, and two patterns of chronic multimorbidity were identified: cardiopulmonary-mental-degenerative disorder pattern (overall prevalence, 58.2%), and cerebrovascular-metabolic disorder pattern (62.6%). Prevalence of the cardiopulmonary-mental-degenerative disorder pattern increased with age, and was higher in men than women; whereas prevalence of the cerebrovascular-metabolic disorder pattern was higher in women than in men but did not vary by age. Conclusion Chronic multimorbidity was highly prevalent among older Chinese adults living in rural areas, and there were specific patterns of the co-occurrence of chronic diseases. Effort is needed to identify possible preventative strategies based on the potential clustering of chronic diseases.

  • 3735.
    Wang, Xiao
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Zhang, Ding
    Sjölinder, Mikael
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Wan, Yi
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Sjölinder, Hong
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Mälar Hospital, Sweden.
    CD46 accelerates macrophage-mediated host susceptibility to meningococcal sepsis in a murine model2017In: European Journal of Immunology, ISSN 0014-2980, E-ISSN 1521-4141, Vol. 47, no 1, p. 119-130Article in journal (Refereed)
    Abstract [en]

    CD46, a membrane cofactor expressed on all nucleated human cells, plays an essential role in suppressing autoimmune reactions and protecting host cells from complement-mediated attack. Human transgenic CD46 homozygousmice (CD46(+/+)) are prone to lethal sepsis upon infection with Neisseria meningitidis (N. meningitidis). However, the underlying mechanisms are poorly understood. Here, we determined thatCD46(+/+) mice produce large numbers of M1 type macrophages with enhanced surface expression of MHC II and production of pro-inflammatory mediators such as IL-6, TNF, IL-12, and IL-1 beta In the presence of M-CSF or GM-CSF, CD46 signaling enhances monocyte-macrophage differentiation. Additionally, CD46(+/+) macrophages rapidly undergo apoptosis upon LPS challenge or meningococcal infection, which could contribute to uncontrolled bacterial dissemination in vivo. Adoptive transfer of CD46(+/+) peritoneal macrophages aggravated septic responses in wild-type mice, but the depletion of macrophages partially alleviated septic reactions in CD46(+/+) mice after N. meningitidis infection. Our findings reveal a novel role of CD46 in accelerating inflammatory responses upon meningococcal infection or LPS stimulation by regulating the functional polarization and survival of macrophages.

  • 3736.
    Wang, Yanling
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Fälting, Johanna M.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Mattsson, Charlotte L.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Holmström, Therese E.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Nedergaard, Jan
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    In brown adipocytes, adrenergically induced beta(1)-/beta(3)-(G(s))-, alpha(2)-(G(i))- and alpha(1)-(G(q))-signalling to Erk1/2 activation is not mediated via EGF receptor transactivation2013In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 319, no 17, p. 2718-2727Article in journal (Refereed)
    Abstract [en]

    Brown adipose tissue is unusual in that the neurotransmitter norepinephrine influences cell destiny in ways generally associated with effects of classical growth factors: regulation of cell proliferation, of apoptosis, and progression of differentiation. The norepinephrine effects are mediated through G-protein-coupled receptors; further mediation of such stimulation to e.g. Erk1/2 activation is in cell biology in general accepted to occur through transactivation of the EGF receptor (by external or internal pathways). We have examined here the significance of such transactivation in brown adipocytes. Stimulation of mature brown adipocytes with cirazoline (alpha(1)-adrenoceptor coupled via G(q)), clonidine (alpha(2) via G(i)) or CL316243 (beta(3) via G(s)) or via beta(1)-receptors significantly activated Erk1/2. Pretreatment with the EGF receptor kinase inhibitor AG1478 had, remarkably, no significant effect on Erk1/2 activation induced by any of these adrenergic agonists (although it fully abolished EGF-induced Erk1/2 activation), demonstrating absence of EGF receptor-mediated transactivation. Results with brown preadipocytes (cells in more proliferative states) were not qualitatively different. Joint stimulation of all adrenoceptors with norepinephrine did not result in synergism on Erk1/2 activation. AG1478 action on EGF-stimulated Erk1/2 phosphorylation showed a sharp concentration response relationship (IC50 0.3 mu M); a minor apparent effect of AG1478 on norepinephrine-stimulated Erk1/2 phosphorylation showed nonspecific kinetics, implying caution in interpretation of partial effects of AG1478 as reported in other systems. Transactivation of the EGF receptor is clearly not a universal prerequisite for coupling of G-protein coupled receptors to Erk1/2 signalling cascades.

  • 3737. Wang, Zhida
    et al.
    Bao, Cuiping
    Su, Cheng
    Xu, Weili
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Luo, Hongbin
    Chen, Liming
    Qi, Xiuying
    Association between diabetes or antidiabetic therapy and lung cancer: A meta-analysis2013In: JOURNAL OF DIABETES INVESTIGATION, ISSN 2040-1116, Vol. 4, no 6, p. 659-666Article in journal (Refereed)
    Abstract [en]

    Aims/IntroductionDiabetes can increase the risk of cancers at several sites, but the association between diabetes and lung cancer remains unclear. We aimed to provide the quantitative estimates for the association between diabetes or antidiabetic treatment and lung cancer risk in the present meta-analysis. Materials and MethodsCohort studies were identified by searching the PubMed database (January 1960 through October 2012) and manually assessing the cited references in the retrieved articles. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a random-effects model. Study quality was assessed using the Newcastle-Ottawa scale. ResultsA total of 19 cohort studies were included in the present meta-analysis. Of these, 14 studies focused on the association between diabetes and lung cancer incidence, and seven studies focused on the association between antidiabetic treatment and lung cancer incidence. Compared with non-diabetic individuals, diabetic patients do not have an increased risk of lung cancer (RR=1.04, 95% CI 0.87-1.24). The association between diabetes and lung cancer remained not statistically significant in subgroup analysis stratified by study characteristics, study quality, diabetes ascertainment or important confounders. A null association between insulin or biguanides therapy and lung cancer risk was found. However, the diabetic patients receiving thiazolidinedione (TZD) treatment had a 20% reduced risk of lung cancer than those without TZD treatment. ConclusionsNo association between diabetes and lung cancer risk was found. However, TZD treatment might reduce lung cancer risk in diabetic patients.

  • 3738. Wangsell, Fredrik
    et al.
    Nordeman, Patrik
    Savmarker, Jonas
    Emanuelsson, Rikard
    Jansson, Katarina
    Lindberg, Jimmy
    Rosenquist, Asa
    Samuelsson, Bertil
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Larhed, Mats
    Investigation of alpha-phenylnorstatine and alpha-benzylnorstatine as transition state isostere motifs in the search for new BACE-1 inhibitors2011In: Bioorganic & Medicinal Chemistry, ISSN 0968-0896, E-ISSN 1464-3391, Vol. 19, no 1, p. 145-155Article in journal (Refereed)
    Abstract [en]

    Inhibition of the BACE-1 protease enzyme has over the recent decade developed into a promising drug strategy for Alzheimer therapy. In this report, more than 20 new BACE-1 protease inhibitors based on alpha-phenylnorstatine, alpha-benzylnorstatine, iso-serine, and beta-alanine moieties have been prepared. The inhibitors were synthesized by applying Fmoc solid phase methodology and evaluated for their inhibitory properties. The most potent inhibitor, tert-alcohol containing (R)-12 (IC(50) = 0.19 mu M) was co-crystallized in the active site of the BACE-1 protease, furnishing a novel binding mode in which the N-terminal amine makes a hydrogen bond to one of the catalytic aspartic acids.

  • 3739. Wanschers, Bas F. J.
    et al.
    Szklarczyk, Radek
    van den Brand, Mariel A. M.
    Jonckheere, An
    Suijskens, Janneke
    Smeets, Roel
    Rodenburg, Richard J.
    Stephan, Katharina
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Helland, Ingrid B.
    Elkamil, Areej
    Rootwelt, Terje
    Ott, Martin
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    van den Heuvel, Lambert
    Nijtmans, Leo G.
    Huynen, Martijn A.
    A mutation in the human CBP4 ortholog UQCC3 impairs complex III assembly, activity and cytochrome b stability2014In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 23, no 23, p. 6356-6365Article in journal (Refereed)
    Abstract [en]

    Complex III (cytochrome bc(1)) is a protein complex of the mitochondrial inner membrane that transfers electrons from ubiquinol to cytochrome c. Its assembly requires the coordinated expression of mitochondrial-encoded cytochrome b and nuclear-encoded subunits and assembly factors. Complex III deficiency is a severe multisystem disorder caused by mutations in subunit genes or assembly factors. Sequence-profile-based orthology predicts C11orf83, hereafter named UQCC3, to be the ortholog of the fungal complex III assembly factor CBP4. We describe a homozygous c.59T > A missense mutation in UQCC3 from a consanguineous patient diagnosed with isolated complex III deficiency, displaying lactic acidosis, hypoglycemia, hypotonia and delayed development without dysmorphic features. Patient fibroblasts have reduced complex III activity and lower levels of the holocomplex and its subunits than controls. They have no detectable UQCC3 protein and have lower levels of cytochrome b protein. Furthermore, in patient cells, cytochrome b is absent from a high-molecular-weight complex III. UQCC3 is reduced in cells depleted for the complex III assembly factors UQCC1 and UQCC2. Conversely, absence of UQCC3 in patient cells does not affect UQCC1 and UQCC2. This suggests that UQCC3 functions in the complex III assembly pathway downstream of UQCC1 and UQCC2 and is consistent with what is known about the function of Cbp4 and of the fungal orthologs of UQCC1 and UQCC2, Cbp3 and Cbp6. We conclude that UQCC3 functions in complex III assembly and that the c.59T > A mutation has a causal role in complex III deficiency.

  • 3740. Warnoff, Carin
    et al.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Hemmingsson, Tomas
    Sorjonen, Kimmo
    Melin, Bo
    Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Is poor self-rated health associated with low-grade inflammation in 43 110 late adolescent men of the general population? A cross-sectional study2016In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 6, no 4, article id e009440Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Self-rated health is a powerful predictor of long-term health and mortality, hence the importance of a better understanding of its biological determinants. Previous studies have shown that low-grade inflammation is associated with poor self-rated health in clinical and healthy populations, but the evidence is sparse in men and completely lacking for men in late adolescence. The aim of this study was to investigate the association between low-grade inflammation and self-rated health among conscripts. It was hypothesised that high levels of inflammatory factors would be associated with poor self-rated health.

    DESIGN: Data from 49 321 men (18-21 years) conscripted for military service in 1969 and 1970 were used. Inflammation had been measured through erythrocyte sedimentation rate (ESR). Self-rated health had been assessed on a five-point scale, and was dichotomised into Good ('Very good'/'Good'/'Fair') versus Poor ('Poor'/'Very poor'). Data from 43 110 conscripts with normal levels of ESR, and who reported self-rated health remained after exclusion of those with ESR <1 and >11 mm/h. Associations were calculated using logistic regression analyses. Adjustments were made for body mass index, socioeconomic position, inflammatory disease, emotion regulation, smoking, risky use of alcohol and physical activity.

    RESULTS: High levels of ESR were associated with higher odds for poor self-rated health (OR: 1.077 for each unit mm/h increase in ESR, 95% CI 1.049 to 1.105).

    CONCLUSIONS: The present study shows for the first time a significant association between a marker of inflammation and self-rated health in late adolescent men, adding to evidence of an association between low-grade inflammation and subjective health perception also in men, as previously demonstrated in women. Further support for inflammation as part of a general psychobiological process that underpins subjective health perception is hereby provided.

  • 3741.
    Wastesson, J. W.
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Ringbäck Weitoft, G.
    Johnell, K.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Educational disparities in antipsychotic drug use among older people with and without dementia in Sweden2015In: Acta Psychiatrica Scandinavica, ISSN 0001-690X, E-ISSN 1600-0447, Vol. 132, no 1, p. 20-28Article in journal (Refereed)
    Abstract [en]

    Objective: Antipsychotic drugs are commonly used to treat behavioural and psychological symptoms of dementia. The aim was to investigate if socioeconomic position was associated with antipsychotic drug treatment among older adults with and without dementia. Method: By record linkage of the Swedish Prescribed Drug Register, Patient Register, and Educational Register, we obtained information on antipsychotics, dementia status, and educational level for 641566 persons aged 75-89year old in Sweden 2005. Results: Among persons diagnosed with dementia (n=32092), 21% used antipsychotics compared with 4% in the total sample (n=641566). Lower education was associated with a higher probability of antipsychotic use in the total sample (adjusted odds ratio [OR] low vs. high education: 1.56; 95% confidence interval [CI]: 1.48-1.64). In the dementia subpopulation, lower education was also associated with a higher likelihood of use of antipsychotics (adjusted ORlow vs. high 1.43; 95% CI: 1.28-1.59). Conclusion: People with dementia were five times more likely to use antipsychotic drugs than the general population of older adults. Also, lower education was associated with a higher use of antipsychotics, both in the general population and in the subgroup of persons with dementia. This finding highlights the importance of investigating healthcare inequalities also among cognitively impaired older adults.

  • 3742.
    Wastesson, Jonas W.
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). University of Southern Denmark, Denmark.
    Canudas-Romo, Vladimir
    Lindahl-Jacobsen, Rune
    Johnell, Kristina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Remaining Life Expectancy With and Without Polypharmacy: A Register-Based Study of Swedes Aged 65 Years and Older2016In: Journal of the American Medical Directors Association, ISSN 1525-8610, E-ISSN 1538-9375, Vol. 17, no 1, p. 31-35Article in journal (Refereed)
    Abstract [en]

    Objectives: To investigate the remaining life expectancy with and without polypharmacy for Swedish women and men aged 65 years and older. Design: Age-specific prevalence of polypharmacy from the nationwide Swedish Prescribed Drug Register (SPDR) combined with life tables from Statistics Sweden was used to calculate the survival function and remaining life expectancy with and without polypharmacy according to the Sullivan method. Setting: Nationwide register-based study. Participants: A total of 1,347,564 individuals aged 65 years and older who had been prescribed and dispensed a drug from July 1 to September 30, 2008. Measurements: Polypharmacy was defined as the concurrent use of 5 or more drugs. Results: At age 65 years, approximately 8 years of the 20 remaining years of life (41%) can be expected to be lived with polypharmacy. More than half of the remaining life expectancy will be spent with polypharmacy after the age of 75 years. Women had a longer life expectancy, but also lived more years with polypharmacy than men. Discussion: Older women and men spend a considerable proportion of their lives with polypharmacy. Conclusion: Given the negative health outcomes associated with polypharmacy, efforts should be made to reduce the number of years older adults spend with polypharmacy to minimize the risk of unwanted consequences.

  • 3743.
    Wastesson, Jonas W.
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Cedazo Minguez, Angel
    Fastbom, Johan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Maioli, Silvia
    Johnell, Kristina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    The composition of polypharmacy: A register-based study of Swedes aged 75 years and older2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 3, article id e0194892Article in journal (Refereed)
    Abstract [en]

    Background Polypharmacy is common among older adults. However, little is known about the composition of polypharmacy: which are the most frequently used drugs, and how much do these drugs contribute to the overall prevalence of polypharmacy. Methods A total of 822,619 Swedes aged >= 75 years was identified from the Total Population Register. Through record-linkage with the Swedish Prescribed Drug Register and the Social Services Register we could analyze concurrent drug use in the entire population (both individuals living in the community and institution) on the 31 December 2013. Results The prevalence of polypharmacy (>= 5 drugs) was 45%. The most frequently used drugs were cardiovascular drugs, analgesics, and psychotropics. By excluding the ten most frequently used drug classes or compounds, the prevalence of polypharmacy was reduced by 69% and 51% respectively. The majority of the users of either one of the 10 most frequently used drugs concurrently used at least 4 other drug classes (66%-85%). Conclusion Almost half of the individuals aged >= 75 years are exposed to polypharmacy in Sweden. A handful of drugs make a large contribution to the overall prevalence of polypharmacy and the majority of drugs prescribed to persons aged >= 75 years are used in combination with other drugs. This highlights the high use of drugs, and the need to consider other concurrent drug treatments when prescribing for older adults.

  • 3744.
    Wastesson, Jonas W.
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Fastbom, Johan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Johnell, Kristina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Expanding the Proportion of Life With Polypharmacy in Sweden: 2006-20132016In: Journal of the American Medical Directors Association, ISSN 1525-8610, E-ISSN 1538-9375, Vol. 17, no 10, p. 957-958Article in journal (Refereed)
  • 3745.
    Wastesson, Jonas W.
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Fastbom, Johan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Ringbäck Weitoft, Gunilla
    Fors, Stefan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Johnell, Kristina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Socioeconomic inequalities in access to specialized psychotropic prescribing among older Swedes: a register-based study2014In: European Journal of Public Health, ISSN 1101-1262, E-ISSN 1464-360X, Vol. 24, no 6, p. 991-996Article in journal (Refereed)
    Abstract [en]

    Background: Mental disorders among older adults are mainly treated with psychotropic drugs. Few of these drugs are, however, prescribed by specialized geriatricians or psychiatrists, but rather from general practitioners (GPs). Socioeconomic inequalities in access to specialist prescribing have been found in younger age groups. Hence, we aimed to investigate whether there are socioeconomic differences in access to geriatrician and psychiatrist prescribing of psychotropic drugs among older adults. Methods: By record-linkage of The Swedish Prescribed Drug Register and The Swedish Education Register, we obtained information for persons aged 75-89 years who had filled a prescription for psychotropic drugs (antipsychotics, anxiolytics, hypnotic/sedatives or antidepressants) with information on prescriber specialty from July to October 2005 (n = 221 579). Multinomial regression analysis was used to investigate whether education was associated with geriatrician and psychiatrist prescribing of psychotropic drugs. Results: The vast majority of the psychotropic drugs were prescribed by 'GPs and other specialists' (similar to 95% GPs). Older adults with higher educational level were more likely to be prescribed psychotropic drugs from psychiatrists and geriatricians. However, after adjustment for place of residence, the association between patient's education and prescription by a geriatrician disappeared, whereas the association with seeing a psychiatrist was only attenuated. Conclusion: Access to specialized prescribing of psychotropics is unequally distributed between socioeconomic groups of older adults in Sweden. This finding was partially confounded by place of residence for geriatrician but not for psychiatrist prescribing. Further research should examine if inequalities in specialized psychotropic prescribing translate into worse outcomes for socioeconomically deprived and non-metropolitan-living older individuals.

  • 3746.
    Wastesson, Jonas W.
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Fors, Stefan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Parker, Marti G.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Johnell, Kristina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Inequalities in health care use among older adults in Sweden 1992-2011: A repeated cross-sectional study of Swedes aged 77 years and older.2014In: Scandinavian Journal of Public Health, ISSN 1403-4948, E-ISSN 1651-1905, Vol. 42, no 8, p. 795-803Article in journal (Refereed)
    Abstract [en]

    AIMS: In the last decades, the Swedish health care system was reformed to promote free choice; however, it has been questioned whether older adults benefit from these reforms. It has also been proposed that reforms promoting free choice might increase inequalities in health care use. Thus, the aim of this study is to investigate socioeconomic differences in health care use among older adults in Sweden, from 1992 to 2011.

    METHODS: The Swedish Panel Study of the Living Conditions of the Oldest Old (SWEOLD) is a nationally representative study of Swedes over 76 years old, including both institutionalized and community-dwelling persons. We analyzed cross-sectional data from SWEOLD waves in 1992, 2002 and 2011 (n ≈ 600/wave); and performed multivariate analyses to investigate whether socioeconomic position was associated with health care use (inpatient, outpatient and dental services) after need was accounted for.

    RESULTS: For the period of 1992-2011, we found that higher education was associated with more use of outpatient and dental care, both before and after adjustment for need. The association between education and inpatient or outpatient care use did not change over time. There was an increase in the proportion of older adults whom used dental care over the 19-year period, and there was a tendency for the socioeconomic differences regarding dentist visits to decrease over time.

    CONCLUSIONS: Our study covering 19 years showed relatively stable findings for socioeconomic differences in health care use among older adults in Sweden. We found there was a slight decrease in inequality in dental care; but unchanged socioeconomic differences in outpatient care, regardless of the changes that occurred in the Swedish health care system.

  • 3747.
    Wastesson, Jonas W.
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Parker, Marti G.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Fastbom, Johan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Thorslund, Mats
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Johnell, Kristina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Drug use in centenarians compared with nonagenarians and octogenarians in Sweden: a nationwide register-based study2012In: Age and Ageing, ISSN 0002-0729, E-ISSN 1468-2834, Vol. 41, no 2, p. 218-224Article in journal (Refereed)
    Abstract [en]

    Background: the number of centenarians increases rapidly. Yet, little is known about their health and use of medications. Objective: to investigate pharmacological drug use in community-dwelling and institutionalised centenarians compared with nonagenarians and octogenarians. Methods: we analysed data on dispensed drugs for centenarians (n = 1,672), nonagenarians (n = 76,584) and octogenarians (n = 383,878) from the Swedish Prescribed Drug Register, record-linked to the Swedish Social Services Register. Multivariate logistic regression analysis was used to analyse whether age was associated with use of drugs, after adjustment for sex, living situation and co-morbidity. Results: in the adjusted analysis, centenarians were more likely to use analgesics, hypnotics/sedatives and anxiolytics, but less likely to use antidepressants than nonagenarians and octogenarians. Moreover, centenarians were more likely to use high-ceiling diuretics, but less likely to use beta-blockers and ACE-inhibitors. Conclusions: centenarians high use of analgesics, hypnotics/sedatives and anxiolytics either reflects a palliative approach to drug treatment in centenarians or that pain and mental health problems increase into extreme old age. Also, centenarians do not seem to be prescribed cardiovascular drug therapy according to guidelines to the same extent as nonagenarians and octogenarians. Whether this reflects an age or cohort effect should be evaluated in longitudinal studies.

  • 3748.
    Wastesson, Jonas W.
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Ringbäck Weitoft, Gunilla
    Parker, Marti G.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Johnell, Kristina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Educational level and use of osteoporosis drugs in elderly men and women: a Swedish nationwide register-based study2013In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 24, no 2, p. 433-442Article in journal (Refereed)
    Abstract [en]

    We examined educational disparities in use of osteoporosis drugs in a nationwide population of Swedes aged 75-89 years old. Individuals with high education were more likely to receive osteoporosis drug treatment than lower educated individuals, particularly among women. INTRODUCTION: This study aims to investigate whether educational level is associated with use of osteoporosis drugs in the general population of older men and women in Sweden, also after adjustment for fractures. METHODS: By record linkage of The Swedish Prescribed Drug Register, The Swedish Patient Register, and The Swedish Education Register, we obtained information on filling of prescriptions for osteoporosis drugs (bisphosphonates, calcium/vitamin D combinations, and selective estrogen receptor modulators) from July to October 2005, osteoporotic fractures from 1998 to 2004, and educational level for 645,429 people aged 75-89 years. Multivariate logistic regression analysis was used to investigate whether education was associated with use of osteoporosis drug therapy. RESULTS: Higher education was associated with use of osteoporosis drugs for both men [odds ratio (OR)(high education vs low), 1.27; 95% confidence interval (CI), 1.19-1.35] and women (OR(high education vs low), 1.57; 95% CI, 1.52-1.61), after adjustment for age, osteoporotic fractures, and comorbidity (i.e., number of other drugs). Among those who had sustained a fracture (n = 57,613), the educational differences in osteoporosis drug treatment were more pronounced in women than men. Further, women were more likely to receive osteoporosis drug treatment after osteoporotic fracture. CONCLUSION: Uptake of osteoporosis drug therapy seems to be unequally distributed in the elderly population, even in a country with presumably equal access to health care.

  • 3749.
    Watling, Christopher N.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Queensland University of Technology, Australia.
    Drivers' perceived legitimacy of enforcement practices for sleep-related crashes: What are the associated factors?2018In: Journal of Forensic and Legal Medicine, ISSN 1752-928X, E-ISSN 1878-7487, Vol. 54, p. 34-38Article in journal (Refereed)
    Abstract [en]

    The purpose of traffic law enforcement is to deter risky driving behaviours. The aim of this study was to examine the individual factors of demographic, personality constructs, and attitudes for their association with perceived legitimacy of traffic law enforcement of sleep-related crashes. In total, 293 drivers completed a survey that assessed perceived legitimacy of enforcement and attitudes towards sleepy driving, as well as individual factors of demographic, personality and risk taking factors. The results demonstrate that younger drivers, drivers with higher levels of extraversion, and those with tolerant attitudes towards sleepy driving were less likely to agree that it is legitimate to charge someone if they crash due to sleepiness. The attitudes towards sleepy driving variable had the largest association with perceived legitimacy. Thus, the factors associated with perceived legitimacy of traffic law enforcement of sleep-related crashes are multifaceted. Overall, the findings have relevance with attitudinal and behaviour change programs, particularly with younger drivers.

  • 3750.
    Watling, Christopher N.
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Queensland University of Technology, Australia.
    Armstrong, Kerry A.
    Radun, Igor
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. University of Helsinki, Finland.
    Examining signs of driver sleepiness, usage of sleepiness countermeasures and the associations with sleepy driving behaviours and individual factors2015In: Accident Analysis and Prevention, ISSN 0001-4575, E-ISSN 1879-2057, Vol. 85, p. 22-29Article in journal (Refereed)
    Abstract [en]

    The impairing effect from sleepiness is a major contributor to road crashes. The ability of a sleepy driver to perceive their level of sleepiness is an important consideration for road safety as well as the type of sleepiness countermeasure used by drivers as some sleepiness countermeasures are more effective than others. The aims of the current study were to determine the extent that the signs of driver sleepiness were associated with sleepy driving behaviours, as well as determining which individual factors (demographic, work, driving, and sleep-related factors) were associated with using a roadside or in-vehicle sleepiness countermeasure. A sample of 1518 Australian drivers from the Australian State of New South Wales and the neighbouring Australian Capital Territory took part in the study. The participants' experiences with the signs of sleepiness were reasonably extensive. A number of the early signs of sleepiness (e.g., yawning, frequent eye blinks) were related with continuing to drive while sleepy, with the more advanced signs of sleepiness (e.g., difficulty keeping eyes open, dreamlike state of consciousness) associated with having a sleep-related close call. The individual factors associated with using a roadside sleepiness countermeasure included age (being older), education (tertiary level), difficulties getting to sleep, not continuing to drive while sleepy, and having experienced many signs of sleepiness. The results suggest that these participants have a reasonable awareness and experience with the signs of driver sleepiness. Factors related to previous experiences with sleepiness were associated with implementing a roadside countermeasure. Nonetheless, the high proportions of drivers performing sleepy driving behaviours suggest that concerted efforts are needed with road safety campaigns regarding the dangers of driving while sleepy.

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