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  • 1.
    Abbasi, Alireza
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för fysikalisk kemi, oorganisk kemi och strukturkemi.
    Lindqvist-Reis, Patric
    Eriksson, Lars
    Sandström, Dick
    Lidin, Sven
    Persson, Ingmar
    Sandström, Magnus
    Highly hydrated cations: Deficiency, mobility and coordination of water in crystalline nonahydrated scandium(III), yttrium(III) and lanthanoid(III) trifluoromethanesulfonate2005Ingår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 11, nr 14, s. 4065-4077Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Trivalent lanthanide-like metal ions coordinate nine water oxygen atoms, which form a tricapped trigonal prism in a large number of crystalline hydrates. Water deficiency, randomly distributed over the capping positions, was found for the smallest metal ions in the isomorphous nonahydrated trifluoromethanesulfonates, [M(H2O)(n)]CF3SO3)(3), in which M=Sc-III, Lu-III, Yb-III, Tm-III or Er-III. The hydration number n increases (n=8.0(1), 8.4(1), 8.7(1), 8.8(1) and 8.96(5), respectively) with increasing ionic size. Deuterium (H-2) solid-state NMR spectroscopy revealed fast positional exchange between the coordinated capping and prism water molecules; this exchange started at temperatures higher than about 280 K for lutetium(m) and below 268 K for scandium(m). Similar positional exchange for the fully nonahydrated yttrium(m) and lanthanum(m) compounds started at higher temperatures, over about 330 and 360 K, respectively. An exchange mechanism is proposed that can exchange equatorial and capping water molecules within the restrictions of the crystal lattice, even for fully hydrated lanthanoid(III) ions. Phase transitions occurred for all the water-deficient compounds at; 185 K. The hydrated scandium(III) trifluoromethanesulfonate transforms reversibly (Delta H degrees= -0.80(1) kJ mol(-1) on cooling) to a trigonal unit cell that is almost nine times larger, with the scandium ion surrounded by seven fully occupied and two partly occupied oxygen atom positions in a distorted capped trigonal prism. The hydrogen bonding to the trifluoromethanesulfonate anions stabilises the trigonal prism of water ligands, even for the crowded hydration sphere of the smallest metal ions in the series. Implications for the Lewis acid catalytic activity of the hydrated scandium(III) and lanthanoid(III) trifluoromethanesulfonates for organic syntheses performed in aqueous media are discussed.

  • 2. Abbo, Catherine
    et al.
    Ekblad, Solvig
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet.
    Waako, Paul
    Okello, Elialilia
    Muhwezi, Wilson
    Musisi, Seggane
    Psychological distress and associated factors among the attendees of traditional healing practices in Jinja and Iganga districts, Eastern Uganda: a cross-sectional study.2008Ingår i: Int J Ment Health Syst, ISSN 1752-4458, Vol. 2, nr 1, s. 16-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Psychological distress and associated factors among the attendees of traditional healing practices in Jinja and Iganga districts, Eastern Uganda: a cross-sectional study.

    Abbo C, Ekblad S, Waako P, Okello E, Muhwezi W, Musisi S.

    Karolinska Institutet, Department of Clinical Neuroscience, Section of Psychiatry, Stockholm, Sweden. cathya180@gmail.com.

    ABSTRACT: BACKGROUND: Mental health problems are a major public health concern worldwide. Evidence shows that African communities, including Uganda, use both modern and traditional healing systems. There is limited literature about the magnitude of psychological distress and associated factors among attendees of traditional healing practices. This study aimed to determine the prevalence and associated factors of psychological distress among attendees of traditional healing practices in two districts in Uganda. METHODS: Face-to-face interviews with the Lusoga version of the Self Reporting Questionnaire (SRQ-20) were carried out with 400 patients over the age of 18 years attending traditional healing in Iganga and Jinja districts in Eastern Uganda. Patients were recruited consecutively in all the traditional healers' shrines that could be visited in the area. Persons with 6 or more positive responses to the SRQ were identified as having psychological distress. Prevalence was estimated and odds ratios of having psychological distress were obtained with multiple logistic regression analysis. RESULTS: 387 questionnaire responses were analyzed. The prevalence of psychological distress in connection with attendance at the traditional healers' shrines was 65.1%. Having a co-wife and having more than four children were significantly associated with psyclogical distress. Among the socioeconomic indicators, lack of food and having debts were significantly associated with psychological distress. The distressed group was more likely to need explanations for ill health. Those who visited both the healer and a health unit were less likely to be distressed. CONCLUSION: This study provides evidence that a substantial proportion of attendees of traditional healing practices suffer from psychological distress. Associated factors include poverty, number of children, polygamy, reason for visiting the healer and use of both traditional healing and biomedical health units. These findings may be useful for policy makers and biomedical health workers for the engagement with traditional healers.

  • 3. Abdallah, Qasem M. A.
    et al.
    Phillips, Roger M.
    Johansson, Fredrik
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Helleday, Thomas
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Cosentino, Laura
    Abdel-Rahman, Hamdy
    Etzad, Jasarat
    Wheelhouse, Richard T.
    Kiakos, Konstantinos
    Bingham, John P.
    Hartley, John A.
    Patterson, Laurence H.
    Pors, Klaus
    Minor structural modifications to alchemix influence mechanism of action and pharmacological activity2012Ingår i: Biochemical Pharmacology, ISSN 0006-2952, E-ISSN 1356-1839, Vol. 83, nr 11, s. 1514-1522Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Alchemix is an exemplar of a class of anthraquinone with efficacy against multidrug resistant tumours. We have explored further the mechanism of action of alchemix and investigated the effect of extending its side arm bearing the alkylating functionality with regard to DNA binding and activity against multidrug resistant cancer cells. Increasing the distance between the intercalating chromophore and the alkylating functionality of ICT2901 (propyl), ICT2902 (butyl) and ICT2903 (pentyl), led to a higher number of DNA alkylation sites, more potent topoisomerase II inhibition and generated more apoptotic and necrotic cells when analysed in p53-proficient HCT116 cells. Intriguingly, alchemix, the compound with the shortest distance between its intercalative chromophore and alkylating functionality (ethyl), did not conform to this SAR. A different toxicity pattern against DNA repair defective CHO cell lines as well as arrest of cells in Cl supports a somewhat distinct mode of action by alchemix compared with its analogues. Importantly, both alchemix and ICT2901 demonstrated greater cytotoxic activity against anthraquinone-resistant MCF-7/adr cells than wild-type MCF-7 cells. Subtle synthetic modification in this anthraquinone series has led to significant changes to the stability of DNA-compound complexes and cellular activity. Given that the failure of chemotherapy in the clinic is often associated with MDR, the results of both alchemix and ICT2901 represent important advances towards improved therapies.

  • 4.
    Abdel Rehim, Abbi
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för analytisk kemi.
    Abdel Rehim, Mohamed
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för analytisk kemi.
    Screening and determination of drugs in human saliva utilizing microextraction by packed sorbent and liquid chromatography-tandem mass spectrometry2013Ingår i: BMC Biomedical chromotography, ISSN 0269-3879, E-ISSN 1099-0801, Vol. 27, nr 9, s. 1188-1191Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This study presents a new method for collecting and handling saliva samples using an automated analytical microsyringe and microextraction by packed syringe (MEPS). The screening and determination of lidocaine in human saliva samples utilizing MEPS and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were carried out. An exact volume of saliva could be collected. The MEPS C-8-cartridge could be used for 50 extractions before it was discarded. The extraction recovery was about 60%. The pharmacokinetic curve of lidocaine in saliva using MEPS-LC-MS/MS is reported.

  • 5. Abdollahi, Abbas
    et al.
    Carlbring, Per
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Klinisk psykologi.
    Coping Style as a Moderator of Perfectionism and Suicidal Ideation Among Undergraduate Students2017Ingår i: Journal of Rational-Emotive & Cognitive-Behavior Therapy, ISSN 0894-9085, E-ISSN 1573-6563, Vol. 35, nr 3, s. 223-239Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Suicide is a serious and growing public health problem and remains an unnecessary cause of death globally. In Iran, the highest prevalence of acute and chronic suicidal ideation is among young people aged 16-24. This study investigates the relationship between coping style, two types of perfectionism, and suicidal ideation among undergraduates, and examines coping style as a moderator of the relationship between perfectionism and suicidal ideation. Multi-stage cluster random sampling was employed to recruit 547 undergraduate students aged 19-24 years from the Islamic Azad University of Karaj. Structural Equation Modelling indicated that suicidal ideation was negatively associated with adaptive perfectionism and task-focused coping but positively associated with emotion-focused coping, avoidance coping, and maladaptive perfectionism. Coping style (including the three styles of task-focused, emotion-focused, and avoidance coping) was found to moderate the relationship between perfectionism and suicidal ideation. The study advances understanding of the importance of coping style in this context and explains how perfectionism affects suicidal ideation.

  • 6.
    Abelein, Axel
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Gräslund, Astrid
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Danielsson, Jens
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Zinc as chaperone-mimicking agent for retardation of amyloid beta peptide fibril formation2015Ingår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 112, nr 17, s. 5407-5412Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Metal ions have emerged to play a key role in the aggregation process of amyloid beta (A beta) peptide that is closely related to the pathogenesis of Alzheimer's disease. A detailed understanding of the underlying mechanistic process of peptide-metal interactions, however, has been challenging to obtain. By applying a combination of NMR relaxation dispersion and fluorescence kinetics methods we have investigated quantitatively the thermodynamic A beta-Zn2+ binding features as well as how Zn2+ modulates the nucleation mechanism of the aggregation process. Our results show that, under near-physiological conditions, substoichiometric amounts of Zn2+ effectively retard the generation of amyloid fibrils. A global kinetic profile analysis reveals that in the absence of zinc A beta(40) aggregation is driven by a monomer-dependent secondary nucleation process in addition to fibril-end elongation. In the presence of Zn2+, the elongation rate is reduced, resulting in reduction of the aggregation rate, but not a complete inhibition of amyloid formation. We show that Zn2+ transiently binds to residues in the N terminus of the monomeric peptide. A thermodynamic analysis supports a model where the N terminus is folded around the Zn2+ ion, forming a marginally stable, short-lived folded A beta(40) species. This conformation is highly dynamic and only a few percent of the peptide molecules adopt this structure at any given time point. Our findings suggest that the folded A beta(40)-Zn2+ complex modulates the fibril ends, where elongation takes place, which efficiently retards fibril formation. In this conceptual framework we propose that zinc adopts the role of a minimal antiaggregation chaperone for A beta(40).

  • 7.
    Abrahamson, Maria
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för socialvetenskaplig alkohol- och drogforskning (SoRAD).
    Moral norms in older Swedish women’s drinking narratives. Enduring patterns and successively new features2012Ingår i: Nordic Studies on Alcohol and Drugs, ISSN 1455-0725, Vol. 29, nr 4, s. 371-396Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS - To examine how the changes in women's relationship to alcohol during the 1960s appear in narratives of situated drinking occasions. DATA - Newly collected autobiographies written by women born between 1918 and 1951 are analysed using theories by William Labov on narrative construction and Kenneth Burke on the rhetoric of motives. RESULTS - The historically restrictive attitude to women at all drinking is present in the oldest women's narratives, while the liberalisation of attitudes to alcohol that took place in the 1960s likewise marks the narratives told by the younger women, even though they when writing are of pension able age. With the writers' diminishing age, the norms framing the narratives have changed, from sobriety among the oldest women to controlled moderation among the younger. And yet, the narratives also demonstrate a stable pattern of questioning women's drinking, although the focus has shifted from tasting alcohol at all to the state of becoming intoxicated. CONCLUSIONS - A controlling norm remains in place, which the women have internalised and made their own. The mitigating circumstances and the neutralising explanations that are presented throughout indicate that the women are conscious of the narratives' deviation from the prevailing norm, and show that women take a risk in drinking alcohol. When a woman drinks she risks her femininity.

  • 8.
    Abrahamson, Maria
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för socialvetenskaplig alkohol- och drogforskning (SoRAD).
    Heimdahl, Karin
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för socialvetenskaplig alkohol- och drogforskning (SoRAD).
    Kvinnor dricker för att de mår dåligt - män dricker för att de är män: om könad diskurs i alkoholpolitiska propositioner och utredningar 1965 - 20112012Ingår i: Samhället, alkoholen och drogerna: politik, konstruktioner och dilemman / [ed] Jessica Storbjörk, Stockholm: Stockholms universitets förlag, 2012, s. 104-129Kapitel i bok, del av antologi (Övrigt vetenskapligt)
  • 9.
    Abrahamson, Maria
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för socialvetenskaplig alkohol- och drogforskning (SoRAD).
    Tryggvesson, Kalle
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för socialvetenskaplig alkohol- och drogforskning (SoRAD).
    Socialtjänstens användning av standardiserade klientbedömningsinstrument – ASI som retorik och praktik i två svenska kommuner2009Ingår i: Nordic Studies on Alcohol and Drugs, ISSN 1455-0725, E-ISSN 1458-6126, Vol. 26, nr 1, s. 21-39Artikel i tidskrift (Refereegranskat)
  • 10.
    Abrahamsson, Klara
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om ojämlikhet i hälsa (CHESS).
    Perceived neighbourhood insecurity and psychosomatic health complaints among adolescents in Stockholm: Exploring district-level and gendered inequalities2016Självständigt arbete på avancerad nivå (masterexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
    Abstract [en]

    The neighbourhood is an essential arena for adolescents’ health development and research suggests that perceived neighbourhood insecurity (PNI) is associated with socio-economic status and self-rated health. The present study explored the distribution of adolescents’ PNI and its association with psychosomatic health complaints across districts. It also examined gender differences and whether family socio-economic position, foreign background and previous exposure to crime could explain part of the association. Data came from classroom-surveys within Stockholm municipality’s 14 districts in 2010, 2012 and 2014 (n=10,291). Linear and logistic multilevel regression models were applied. Results showed that the average level of PNI varied considerably between districts and were strongly connected to its socio-demographic composition. However, individual characteristics in terms of family background and previous exposure to crime only explained a minor part of the variation in PNI across districts. Girls reported more insecurity than boys in all districts. Gender differences in PNI decreased in absolute numbers, but increased in relative numbers, as the overall ‘neighbourhood safety’ increased. Between-district differences in health were minor, but PNI was still a strong predictor of individual-level health, especially for boys. Furthermore, the predictive power of PNI on health was stronger in districts perceived as safer.

  • 11.
    Abramsson-Zetterberg, Lilianne
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Ilback, Nils-Gunnar
    The synthetic food colouring agent Allura Red AC (E129) is not genotoxic in a flow cytometry-based micronucleus assay in vivo2013Ingår i: Food and Chemical Toxicology, ISSN 0278-6915, E-ISSN 1873-6351, Vol. 59, s. 86-89Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The safety of several azo colouring agents, used as food additives, has during the years been questioned. Allura Red AC (E129) has in some publications been classified as genotoxic. In fact, in the European Union, Allura Red is permitted as a food additive in human food, but, surprisingly, it was not acceptable as an additive for use in animal feed. In this study we have evaluated whether Allura Red is genotoxic using a flow cytometer-based micronucleus assay in peripheral blood of mice. Male FVB mice were given a single intra-peritoneal injection of various doses of Allura Red and sacrificed at 46 h after treatment. The tested doses were 0, 100, 200, 400, 600, 800, 1000, 1500, and 2000 mg/kg body weight (b.w.). Each dose group constituted three mice, except for in the dose group of 1000 mg/kg b.w., which constituted four mice. Blood samples were collected and the frequency of micronucleated polychromatic erythrocytes (fMNPCE) and the cell proliferation (%PCE) was determined. The analyses did not show any significant difference in the %PCE or in the fMNPCE. Consequently, under the testing circumstances one can conclude that Allura Red is not genotoxic.

  • 12.
    Abreu-Vieira, Gustavo
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Thermal physiology and metabolism: Interplay between heat generation and energy homeostasis2015Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Mammal metabolism is intimately connected to the maintenance of body temperature. While metabolic pathways invariably produce heat as a by-product, the natural heat present in the environment also plays a role in defining the adaptive metabolism and general physiology of an organism. This thesis aims to discuss basic aspects of energy expenditure and their interactions with energy stores and body composition. In Paper I, we apply a new technique – high-resolution laser-Doppler imaging – to describe physiological regulatory features of adrenergically-stimulated blood flow in brown adipose tissue, and evaluate the validity of blood flow as a parameter to estimate nonshivering thermogenesis. Paper II focuses on the central regulation of body temperature. In the absence of bombesin receptor subtype-3, mice present an altered neurological body temperature setpoint, while peripheral thermogenic capacity remains intact. We conclude that brown adipose tissue malfunction is not the cause of the hypothermia observed in this mouse model. Paper III incorporates measurements of body temperature to the energy expenditure of different sources: basal metabolic rate, physical activity, thermic effect of food, and cold-induced thermogenesis. We describe basic aspects of dynamic insulation, energetic costs of circadian variation and hypothesize that physical activity may change the body temperature setpoint. Paper IV describes methodological issues related to glucose tolerance tests in obese mice. We conclude that the erroneous scaling of doses may affect the interpretation of metabolic health in mouse models, and suggest a new methodology. Paper V describes the outcomes caused by the expression of the human Cidea protein in adipose tissue of mice and suggests that this protein may clarify the link between adipose tissue expansion and healthy obesity. Paper VI explores the dissociation between thiazolidinedione-induced adipose tissue “browning” and reduced blood glycaemia. We demonstrate that although this pharmacological class tends to induce some level of brown adipose tissue recruitment, this phenomenon does not define its antidiabetic effects.

  • 13.
    Abreu-Vieira, Gustavo
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Fischer, Alexander W.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. University of Hamburg, Germany.
    Mattsson, Charlotte
    de Jong, Jasper M. A.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Shabalina, Irina G.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Ryden, Mikael
    Laurencikiene, Jurga
    Arner, Peter
    Cannon, Barbara
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Nedergaard, Jan
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Petrovic, Natasa
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Cidea improves the metabolic profile through expansion of adipose tissue2015Ingår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 6, artikel-id 7433Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In humans, Cidea (cell death-inducing DNA fragmentation factor alpha-like effector A) is highly but variably expressed in white fat, and expression correlates with metabolic health. Here we generate transgenic mice expressing human Cidea in adipose tissues (aP2-hCidea mice) and show that Cidea is mechanistically associated with a robust increase in adipose tissue expandability. Under humanized conditions (thermoneutrality, mature age and prolonged exposure to high-fat diet), aP2-hCidea mice develop a much more pronounced obesity than their wild-type littermates. Remarkably, the malfunctioning of visceral fat normally caused by massive obesity is fully overcome-perilipin 1 and Akt expression are preserved, tissue degradation is prevented, macrophage accumulation is decreased and adiponectin expression remains high. Importantly, the aP2-hCidea mice display enhanced insulin sensitivity. Our data establish a functional role for Cidea and suggest that, in humans, the association between Cidea levels in white fat and metabolic health is not only correlative but also causative.

  • 14.
    Abreu-Vieira, Gustavo
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Kalinovich, Anastasia
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Cannon, Barbara
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Nedergaard, Jan
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Novel thiazolidinediones distinguish between (UCP1-independent) antidiabetic effects (MSDC-0602) and adipogenic and browning-inducing effects (MSDC-0160) of classical thiazolidinediones (rosiglitazone)Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Thiazolinediones (TZDs), also called glitazones, are a class of drugs traditionally used forimproving glucose tolerance in type II diabetes mellitus. The beneficial effects ofthiazolidinedione are believed to be caused by the drug binding to the nuclear receptor PPARγ,which in turn triggers a general adipogenic program in white adipose tissue, and apparentthermogenic recruitment of brown and brite/beige fat. Here, we present a comparison of thephysiological effects of three thiazolidinediones (rosiglitazone, MSDC-0602, and MSDC-0160)in C57BL/6 mice fed high-fat diet and housed at thermoneutrality. Rosiglitazone and MSDC-0160 caused the classically-described thiazolidinedione effects of increased fat mass,hyperphagia, and increased UCP1 levels in brown adipose tissue. MSDC-0602 and rosiglitazoneimproved glucose tolerance but MSDC-0602 did not induce increased fat mass, hyperphagia, orincreased UCP1 levels in brown fat. The beneficial effects of thiazolidinediones were fullypresent even in UCP1-KO mice, providing evidence for a dissociation between thiazolidinedioneinducedadipose tissue browning and their antidiabetic effects. We conclude that even structurallysimilar thiazolidinediones can act through distinct pathways, and that the glucose-loweringeffects of this class do not seem to rely on PPAR-γ-induced browning of adipose tissues.

  • 15. Acevedo, Nathalie
    et al.
    Bornacelly, Adriana
    Mercado, Dilia
    Unneberg, Per
    Stockholms universitet, Science for Life Laboratory (SciLifeLab). Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Mittermann, Irene
    Valenta, Rudolf
    Kennedy, Malcolm
    Scheynius, Annika
    Caraballo, Luis
    Genetic Variants in CHIA and CHI3L1 Are Associated with the IgE Response to the Ascaris Resistance Marker ABA-1 and the Birch Pollen Allergen Bet v 12016Ingår i: plos one, ISSN 1932-6203, Vol. 11, nr 12, artikel-id e0167453Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Helminth infections and allergic diseases are associated with IgE hyperresponsiveness but the genetics of this phenotype remain to be defined. Susceptibility to Ascaris lumbricoides infection and antibody levels to this helminth are associated with polymorphisms in locus 13q33-34. We aimed to explore this and other genomic regions to identify genetic variants associated with the IgE responsiveness in humans. Forty-eight subjects from Cartagena, Colombia, with extreme values of specific IgE to Ascaris and ABA-1, a resistance marker of this nematode, were selected for targeted resequencing. Burden analyses were done comparing extreme groups for IgE values. One-hundred one SNPs were genotyped in 1258 individuals of two well-characterized populations from Colombia and Sweden. Two low-frequency coding variants in the gene encoding the Acidic Mammalian Chitinase (CHIA rs79500525, rs139812869, tagged by rs10494133) were found enriched in high IgE responders to ABA-1 and confirmed by genetic association analyses. The SNP rs4950928 in the Chitinase 3 Like 1 gene (CHI3L1) was associated with high IgE to ABA-1 in Colombians and with high IgE to Bet v 1 in the Swedish population. CHIA rs10494133 and ABDH13 rs3783118 were associated with IgE responses to Ascaris. SNPs in the Tumor Necrosis Factor Superfamily Member 13b gene (TNFSF13B) encoding the cytokine B cell activating Factor were associated with high levels of total IgE in both populations. This is the first report on the association between low-frequency and common variants in the chitinases- related genes CHIA and CHI3L1 with the intensity of specific IgE to ABA-1 in a population naturally exposed to Ascaris and with Bet v 1 in a Swedish population. Our results add new information about the genetic influences of human IgE responsiveness; since the genes encode for enzymes involved in the immune response to parasitic infections, they could be helpful for understanding helminth immunity and allergic responses. We also confirmed that TNFSF13B has an important and conserved role in the regulation of total IgE levels, which supports potential evolutionary links between helminth immunity and allergic response.

  • 16. Adams, John
    et al.
    Pike, Tim
    Corna, Laurie M.
    Platts, Loretta G.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet.
    Worts, Diana
    McDonough, Peggy
    Di Gessa, Giorgio
    Sacker, Amanda
    Glaser, Karen
    Price, Debora
    How do female lifecourses affect income in retirement?2016Rapport (Övrigt vetenskapligt)
    Abstract [en]

    This Briefing Note examines the influence of various lifecourses on income in retirement. The primary focus of this note is to consider how women’s retirement income is affected by motherhood. This includes the impact of taking time out of work to care for children, as well as the implications of the Motherhood Penalty, which is the observation that mothers tend to have reduced incomes relative to women without children.

  • 17.
    Adamus-Gorka, Magdalena
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Medicinsk strålningsfysik (tills m KI).
    Mavroidis, Panayiotis
    Stockholms universitet, Naturvetenskapliga fakulteten, Medicinsk strålningsfysik (tills m KI).
    Brahme, Anders
    Stockholms universitet, Naturvetenskapliga fakulteten, Medicinsk strålningsfysik (tills m KI).
    Lind, Bengt K
    Stockholms universitet, Naturvetenskapliga fakulteten, Medicinsk strålningsfysik (tills m KI).
    An “Effective functional subunit size” model for the dose response of rat spinal cord paralysis2007Ingår i: 13th International Congress of Radiation Research, San Fransisco, USA, July 8-12, 2007, 2007Konferensbidrag (Övrig (populärvetenskap, debatt, mm))
    Abstract [en]

    Background: Radiobiological models for normal tissue complication probability (NTCP) are more and more commonly used in order to estimate the clinical outcome of radiation therapy. A normal tissue complication probability model to be considered a good and reliable one should fulfill the following two requirements: (a) it should predict the sigmoid shape of the dose-response curve as well as possible and (b) it should duly handle the volume effect. In the work from 2005 (IJROBP 61(3):892-900, 2005) P. van Luijk et al. suggest that none of the existing NTCP models is able to describe the volume effects present in the rat spinal cord during irradiation with small proton beams and they indicate the need for developing such new models.

    Methods: We have used the experimental data from H. Bijl et al. (IJROBP 52(1):205-211, 2002) to try explaining the change in the fifty percent effective dose (ED50) for different field sizes. We initiated this study to evaluate whether the induction of white matter necrosis in rat spinal cord after irradiation with small proton beams could be explained independent of used NTCP model. We therefore introduced a new concept of effective FSU dose, where a convolution of the original dose distribution with a function describing the effective size of a single FSU results in the average doses in a functional subunit. Such procedure allows determining the ED50 in an FSU of a certain size, within the irradiation field. We have also looked at non uniform dose distributions to see whether using a similar method we can explain the so called “bath and shower experiments” (IJROBP 57(1): 274-281, 2003).

    Results: Using the least square method to compare the effective doses for different sizes of functional subunits with the experimental data we observe the best fit for about 8 mm length. It seems that this length could be understood as an effective size of functional subunits in rat spinal cord, explaining what is otherwise interpreted as a volume effect. For the non uniform dose distributions an effective FSU length of 5 mm gives the optimal fit with the Probit dose-response model.

    Conclusions: The concept of an effective FSU length seems to explain at least part of the effects seen when small portions of the rat spinal cord are irradiated. The most likely FSU length for the shower and bath experiments is 5 mm according to these calculations.

  • 18.
    Addo, Rebecka N.
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Perception och psykofysik. Uppsala University, Sweden.
    Wiens, Stefan
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Perception och psykofysik.
    Nord, Marie
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Perception och psykofysik.
    Larsson, Maria
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Perception och psykofysik.
    Olfactory Functions in Adults With Autism Spectrum Disorders2017Ingår i: Perception, ISSN 0301-0066, E-ISSN 1468-4233, Vol. 46, nr 3-4, s. 530-537Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Autism spectrum disorders (ASD) are often characterized by atypical sensory behavior (hyperor hyporeactivity) although evidence is scarce regarding olfactory abilities in ASD; 16 adults with high-functioning ASD (mean age: 38.2, SD: 9.7) and 14 healthy control subjects (mean age: 42.0 years, SD: 12.5) were assessed in odor threshold, free and cued odor identification, and perceived pleasantness, intensity, and edibility of everyday odors. Although results showed no differences between groups, the Bayes Factors (close to 1) suggested that the evidence for no group differences on the threshold and identification tests was inconclusive. In contrast, there was some evidence for no group differences on perceived edibility (BF01 = 2.69) and perceived intensity (BF01 = 2.80). These results do not provide conclusive evidence for or against differences between ASD and healthy controls on olfactory abilities. However, they suggest that there are no apparent group differences in subjective ratings of odors.

  • 19.
    Adlerz, Linda
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi.
    Processing of the amyloid precursor protein and its paralogues amyloid precursor-like proteins 1 and 22007Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Alzheimer’s disease (AD) is a neurodegenerative disorder which is histopathologically characterised by amyloid plaques and neurofibrillary tangles. Amyloid plaques consist of the amyloid β-peptide (Aβ) that can form aggregates in the brain. Aβ is generated from the amyloid precursor protein (APP) through proteolytic cleavage. APP belongs to a conserved protein family that also includes the two paralogues, APP-like proteins 1 and 2 (APLP1 and APLP2). Despite the immense amount of research on APP, motivated by its implication in AD, the function of this protein family has not yet been determined. In this thesis, we have studied the expression and proteolytic processing of the APP protein family. Our results are consistent with previous findings that suggest a role for APP during neuronal development. Treatment of cells with retinoic acid (RA) resulted in increased synthesis. In addition, we observed that RA treatment shifted the processing of APP from the amyloidogenic to the non-amyloidogenic pathway. The proteins in the APP family have been hard to distinguish both with respect to function and proteolytic processing. However, for development of new drugs with APP processing enzymes as targets this is of great importance. Our studies suggest similarities, but also differences in the mechanism regulating the processing of the different paralogues. We found that brain-derived neurotrophic factor (BDNF) had different impact on the members of the APP family. Most interestingly, we also found that the mechanism behind the increased processing in response to IGF-1 was not identical between the homologous proteins. In summary, our results indicate that in terms of regulation APLP1 and APLP2 differ more from each other than from APP. Our studies open up the possibility of finding means to selectively block Aβ production without interfering with the processing and function of the paralogous proteins.

  • 20.
    Adlerz, Linda
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi.
    Beckman, Marie
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi.
    Holback, Sofia
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi.
    Tehranian, Roya
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi.
    Cortés Toro, Veronica
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi.
    Iverfeldt, Kerstin
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi.
    Accumulation of the amyloid precursor-like protein APLP2 and reduction of APLP1 in retinoic acid-differentiated human neuroblastoma cells upon curcumin-induced neurite retraction2003Ingår i: Brain Research. Molecular Brain Research, ISSN 0169-328X, E-ISSN 1872-6941, Vol. 119, nr 1, s. 62-72Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Amyloid precursor protein (APP) belongs to a conserved gene family, also including the amyloid precursor-like proteins, APLP1 and APLP2. The function of these three proteins is not yet fully understood. One of the proposed roles of APP is to promote neurite outgrowth. The aim of this study was to investigate the regulation of the expression levels of APP family members during neurite outgrowth. We observed that retinoic acid (RA)-induced neuronal differentiation of human SH-SY5Y cells resulted in increased expression of APP, APLP1 and APLP2. We also examined the effect of the NFκB, AP-1 and c-Jun N-terminal kinase inhibitor curcumin (diferuloylmethane) on the RA-induced expression levels of these proteins. We found that treatment with curcumin counteracted the RA-induced mRNA expression of all APP family members. In addition, we observed that curcumin treatment resulted in neurite retraction without any effect on cell viability. Surprisingly, curcumin had differential effects on the APLP protein levels in RA-differentiated cells. RA-induced APLP1 protein expression was blocked by curcumin, while the APLP2 protein levels were further increased. APP protein levels were not affected by curcumin treatment. We propose that the sustained levels of APP and the elevated levels of APLP2, in spite of the reduced mRNA expression, are due to altered proteolytic processing of these proteins. Furthermore, our results suggest that APLP1 does not undergo the same type of regulated processing as APP and APLP2.

  • 21.
    Adlerz, Linda
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi.
    Soomets, Ursel
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi. University of Tartu, Estonia.
    Holmlund, Linda
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi.
    Virland, Saade
    Langel, Ülo
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi.
    Iverfeldt, Kerstin
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi.
    Down-regulation of amyloid precursor protein by peptide nucleic acid oligomer in cultured rat primary neurons and astrocytes2003Ingår i: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 336, nr 1, s. 55-59Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The amyloid precursor protein (APP) and its proteolytic cleavage products, the amyloid P peptides, have been implicated as a cause of Alzheimer's disease. Peptide nucleic acids (PNA), the DNA mimics, have been shown to block the expression of specific proteins at both transcriptional and translational levels. Generally, the cellular uptake of PNA is low. However, recent studies have indicated that the effect of unmodified antisense PNA uptake is more pronounced in nervous tissue. In this study we have shown that biotinylated PNA directed to the initiator codon region of the APP mRNA (-4 - +11) was taken up into the cytoplasm of primary rat cerebellar granule cells and cortical astrocytes, using fluorescence and confocal microscopy studies. Uptake of PNA was faster in neurons than in astrocytes. Western blotting analysis showed that APP was strongly down-regulated in both neurons and astrocytes. Thus, unmodified PNA can be used for studies on the function of APP in neurons and astrocytes.

  • 22.
    Adrian Meredith, Jenny
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Björklund, Catarina
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Adolfsson, Hans
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Edlund, Michael
    Jansson, Katarina
    Lindberg, Jimmy
    Vrang, Lotta
    Hallberg, Anders
    Institutionen för läkemedelskemi, Uppsala universitet.
    Rosenquist, Åsa
    Samuelsson, Bertil
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Design and Synthesis of BACE-1 Inhibitors Containing a New Hydroxyethylene (HE) Scaffold: Potent activities in a cellular assayManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    In a preceding report from our group we disclosed the development of a novel HE transition state isostere with a difluorophenoxymethyl side chain in the P1 position and a methoxy group in the P1’ position furnishing highly potent inhibitors of BACE-1 (i.e. lead compound 1), which moreover exhibit very promising selectivity over cathepsin D. In a continuation of this work with the aim at improving on the cell-based activity and pharmacokinetic properties, we have further developed the SAR for the P1 side chain of inhibitor 1 whereby the P1 side chain oxygen has been substituted for an amine, a carbon or a bond. The chemistry developed for the previous HE inhibitor structure 1 has now been extended to readily accommodate the introduction of new P1 side chains into this new HE scaffold. These modifications have given rise to several highly potent inhibitors where the most potent displayed a BACE-1 Ki value of 0.2 nM and a cell-based Aβ40 IC50 value of 9 nM. Thus, regarding the enzyme inhibition in the cell assay a more than 600-fold improvement compared to compound 1 was achieved via minor structural alterations.

  • 23.
    Adrian Meredith, Jenny
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Björklund, Catarina
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Adolfsson, Hans
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Jansson, Katarina
    Hallberg, Anders
    Institutionen för läkemedelskemi, Uppsala universitet.
    Rosenquist, Åsa
    Samuelsson, Bertil
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    P2’-truncated BACE-1 inhibitors with a novel hydroxethylene-like core2010Ingår i: European Journal of Medicinal Chemistry, ISSN 0223-5234, E-ISSN 1768-3254, Vol. 45, nr 2, s. 542-554Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Highly potent BACE-1 protease inhibitors derived from a novel hydroxyethylene-like core structure were recently developed by our group using X-ray crystal structure data and molecular modelling. In a continuation of this work guided by molecular modelling we have explored a truncated core motif where the P2’ amide group is replaced by an ether linkage resulting in a set of alkoxy, aryloxy and alkylaryl groups, with the overall aim to reduce molecular weight and the number of amide bonds to increase permeability and bestow the inhibitors with drug-like features. The most potent of these inhibitors displayed a BACE-1 IC50 value of 140 nM. The synthesis of these BACE-1 inhibitors utilizes readily available starting materials, furnishing the target compounds in good overall yields.

  • 24.
    Adrian Meredith, Jenny
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Wallberg, Hans
    Vrang, Lotta
    Oscarson, Stefan
    Centre for Synthesis and Chemical Biology, University College Dublin, Belfield, Dublin 4, Ireland.
    Parkes, Kevin
    Hallberg, Anders
    Institutionen för läkemedelskemi, Uppsala universitet.
    Samuelsson, Bertil
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Design and Synthesis of Novel P2 Substituents in Diol-based HIV Protease Inhibitors2010Ingår i: European Journal of Medicinal Chemistry, ISSN 0223-5234, E-ISSN 1768-3254, Vol. 45, nr 1, s. 160-170Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The synthesis and SAR of HIV-1 protease inhibitors containing novel P2 structural elements are presented. The inhibitors were designed having hydrogen bond accepting P2 substituents to probe potential favorable interactions to Asp-29/Asp-30 of the HIV-1 protease backbone utilizing inhibitor 3 as a model template. Several inhibitors were synthesized from an L-Val-methylamide P2 motif by appending hydrogen bonding moieties from either the isopropyl side chain or from the methylamide portion. The most promising inhibitors 4a and 4e displayed Ki values of 1.0 nM and 0.7 nM respectively and EC50 values in the MT4 cell-based assay of 0.17 µM and 0.33 µM respectively, a slight loss in potency compared to lead inhibitor 3. These inhibitors were also tested against an HIV protease inhibitor resistant strain carrying the M46I, V82F, and I84V mutations. Inhibitors 4a and 4e displayed a 3 and 4 fold change respectively compared with HIV wild type, whereas lead inhibitor 3 showed a higher 9 fold change. This study further demonstrate the chemical tractability of the approach where various P2 substituents can be introduced in just one chemical step from lactone x enabling facile modifications of the overall properties in this inhibitor class.

  • 25.
    af Klinteberg, Britt
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om ojämlikhet i hälsa (CHESS).
    Granskaya, J
    Birath Scheffel, C
    Beijer, U
    Tsvetkova, L
    Personality characteristics and perceived health in Russian and Swedish female young adults with alcohol drinking habits2014Ingår i: Personality and Individual Differences, ISSN 0191-8869, E-ISSN 1873-3549, Vol. 60, nr Suppl., s. S64-Artikel i tidskrift (Refereegranskat)
  • 26.
    af Klinteberg, Britt
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om ojämlikhet i hälsa (CHESS). Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Biologisk psykologi. Karolinska Institutet, Sweden.
    Johansson, Sven-Erik
    Levander, Maria
    Alm, Per Olof
    Oreland, Lars
    Smoking habits – Associations with personality/behavior, platelet monoamine oxidase activity and plasma thyroid hormone levels2017Ingår i: Personality and Individual Differences, ISSN 0191-8869, E-ISSN 1873-3549, Vol. 118, s. 71-76Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The objective was to outline results from our scientific studies on the associations among childhood behavior, adult personality, and biochemical factors in smoking habits. The studies consisted of: (1) follow-up of young criminals and controls, subdivided into risk for antisocial behavior groups, based on childhood rating levels of a projective test; and adult smoking habit groups; and (2) a large group of young adults examined on the same inventories. Personality in terms of KSP and EPQ-I scale scores, controlled for intelligence, indicated that the high and very high risk groups displayed significantly higher self-rated impulsiveness, anxiety, and nonconformity, as compared to the low risk group. Further, the very high risk group subjects, found to be overrepresented among subjects with heavy smoking habits, displayed lower mean platelet MAO-B activity and higher thyroid hormone levels than the low risk group. Thus, the higher the childhood risk for antisocial behavior, the clearer the adult personality pattern making subjects more disposed for smoking appeared; and the higher smoking habits, the stronger the relationships with biochemical measures. Results are discussed in terms of possible underlying mechanisms influencing personality and smoking habits.

  • 27.
    Agahi, Neda
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Fors, Stefan
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Fritzell, Johan
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Shaw, Benjamin A.
    Smoking and Physical Inactivity as Predictors of Mobility Impairment During Late Life: Exploring Differential Vulnerability Across Education Level in Sweden2018Ingår i: The journals of gerontology. Series B, Psychological sciences and social sciences, ISSN 1079-5014, E-ISSN 1758-5368, Vol. 73, nr 4, s. 675-683Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: To test whether older adults from high and low educational groups are differentially vulnerable to the impact of smoking and physical inactivity on the progression of mobility impairment during old age.

    Methods: A nationally representative sample of older Swedish adults (n = 1,311), aged 57-76 years at baseline (1991), were followed for up to 23 years (2014). Multilevel regression was used to estimate individual trajectories of mobility impairment over the study period and to test for differences in the progression of mobility impairment on the basis of smoking status, physical activity status, and level of education.

    Results: Compared to nonsmokers, heavy smokers had higher levels and steeper increases in mobility impairment with advancing age. However, there were only small and statistically nonsignificant differences in the impact of heavy smoking on mobility impairment in high versus low education groups. A similar pattern of results was found for physical inactivity.

    Discussion: Differential vulnerability to unhealthy behaviors may vary across populations, age, time-periods, and health outcomes. In this study of older adults in Sweden, low and high education groups did not differ significantly in their associations between heavy smoking or physical inactivity, and the progression of mobility impairment.

  • 28.
    Agahi, Neda
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Kelfve, Susanne
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Sociologiska institutionen. Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Lennartsson, Carin
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Kåreholt, Ingemar
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Jönköping University, Sweden.
    Alcohol consumption in very old age and its association with survival: A matter of health and physical function2016Ingår i: Drug And Alcohol Dependence, ISSN 0376-8716, E-ISSN 1879-0046, Vol. 159, s. 240-245Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Alcohol consumption in very old age is increasing; yet, little is known about the personal and health-related characteristics associated with different levels of alcohol consumption and the association between alcohol consumption and survival among the oldest old. Methods: Nationally representative data from the Swedish Panel Study of Living Conditions of the Oldest Old (SWEOLD, ages 76-101; n=863) collected in 2010/2011 were used. Mortality was analyzed unti12014. Alcohol consumption was measured with questions about frequency and amount. Drinks per month were calculated and categorized as abstainer, light-to-moderate drinker (0.5-30 drinks/month) and heavy drinker (>30 drinks/month). Multinomial logistic regressions and Laplace regressions were performed. Results: Compared to light-to-moderate drinkers, abstainers had lower levels of education and more functional health problems, while heavy drinkers were more often men, had higher levels of education, and no serious health or functional problems. In models adjusted only for age and sex, abstainers died earlier than drinkers. Among light-to-moderate drinkers, each additional drink/month was associated with longer survival, while among heavy drinkers, each additional drink/month was associated with shorter survival. However, after adjusting for personal and health-related factors, estimates were lower and no longer statistically significant. Conclusions: The association between alcohol consumption and survival in very old age seems to have an inverse J-shape; abstention and heavy use is associated with shorter survival compared to light-to moderate drinking. To a large extent, differences in survival are due to differences in baseline health and physical function.

  • 29.
    Agahi, Neda
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Lennartsson, Carin
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Kåreholt, Ingemar
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Shaw, Benjamin
    Trajectories of social activities from middle age to old age and late-life disability: a 36-year follow-up2013Ingår i: Age and Ageing, ISSN 0002-0729, E-ISSN 1468-2834, Vol. 42, nr 6, s. 790-793Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: to examine the association between 34-year trajectories of social activity, from middle age to old age and late-life disability.                  

    Methods: data from the Swedish Level of Living Survey (LNU) and the Swedish Panel Study of the Oldest Old (SWEOLD) were used. LNU data from 1968, 1981, 1991 and 2000 were merged with SWEOLD data from 1992, 2002 and 2004 to create a longitudinal data set  with five observation periods. Trajectories of social activities covered 1968–2002, and late-life disability was measured  in 2004. The sample consisted of 729 individuals aged 33–61 at baseline (1968), who participated in at least four observation periods and who were free from mobility limitations at baseline. Four trajectories of social activity were identified and used as predictors of late-life disability.                  

    Results: reporting low/medium levels of social activity from mid-life to old age was the most common trajectory group. Persons reporting continuously low/medium or decreasing levels of social activity had higher odds ratios for late-life disability (OR = 2.33 and OR = 2.15, respectively) compared with those having continuously high levels of activity, even when adjusting for age, sex and mobility limitations, and excluding persons with baseline mobility limitations.                  

    Conclusions: results suggest that the disability risk associated with social activities is related to recent levels of activity, but also that risk may accumulate over time, as indicated by the higher disability risk associated with the continuously low/medium level social activity trajectory.

  • 30.
    Agahi, Neda
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Shaw, Benjamin A.
    Smoking trajectories from midlife to old age and the development of non-life-threatening health problems: A 34-year prospective cohort study2013Ingår i: Preventive Medicine, ISSN 0091-7435, E-ISSN 1096-0260, Vol. 57, nr 2, s. 107-112Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. To examine how trajectories of smoking observed over a 34-year period, were associated with the progression of mobility impairment, musculoskeletal pain, and symptoms of psychological distress from midlife to old age. Method. The Swedish Level of Living Survey (LNU) and the Swedish Panel Study of the Oldest Old (SWEOLD) were merged to create a nationally representative longitudinal sample of Swedish adults (aged 30-50 at baseline; n = 1060), with four observation periods, from 1968 through 2002. Five discrete smoking trajectory groups were treated as predictors of variation in health trajectories using multilevel regression. Results. At baseline, there were no differences in mobility impairment between smoking trajectory groups. Over time all smokers, particularly persistent and former heavy smokers, exhibited faster increases in mobility problems compared with persistent non-smokers. Additionally, all smoking groups reported more pain symptoms than the non-smokers, at baseline and over time, but most of these differences did not reach statistical significance. Persistent heavy smokers reported elevated levels of psychological distress at baseline and over time. Conclusion. Smokers, and even some former smokers, who survive into old age appear to be at increased risk for non-life-threatening conditions that can diminish quality of life and increase demands for services.

  • 31.
    Agahi, Neda
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Shaw, Benjamin A.
    Fors, Stefan
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Social and economic conditions in childhood and the progression of functional health problems from midlife into old age2014Ingår i: Journal of Epidemiology and Community Health, ISSN 0143-005X, E-ISSN 1470-2738, Vol. 68, nr 8, s. 734-740Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Childhood living conditions have been found to predict health and mortality in midlife and in old age. This study examines the associations between social and economic childhood conditions and the onset and progression of functional health problems from midlife into old age, and the extent to which potential associations are mediated by educational attainment and smoking. Methods Data from the Level of Living Survey and the Swedish Panel Study of Living Conditions of the Oldest Old were merged to create a longitudinal data set with five repeated measures from 1968 to 2004 (n=1765, aged 30-50 years and free from functional health problems at baseline). Multilevel regression models were used to analyse retrospective reports of social and economic conditions in childhood (eg, conflicts or economic problems in the family) in relation to the progression of functional health problems over the 36-year period. Results Results showed that social and economic disadvantages in childhood were associated with an earlier onset and a faster progression of functional health problems from midlife into old age. Subsequent models showed that differences in educational attainment, but not smoking, explained much of the association between childhood disadvantages and trajectories of functional health problems. Conclusions According to these results, adverse social and economic conditions in childhood affect the development of functional health problems from midlife into old age indirectly through less favourable life careers, including lower education. Creating equal opportunities for educational attainment may help reduce the long-term effects of disadvantaged childhood conditions and postpone functional health problems.

  • 32.
    Agahi, Neda
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Silverstein, Merril
    Parker, Marti G.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Late-Life and Earlier Participation in Leisure Activities: Their Importance for Survival Among Older Persons2011Ingår i: Activities, Adaptation & Aging, ISSN 0192-4788, E-ISSN 1544-4368, Vol. 35, nr 3, s. 210-222Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Is activity participation in old age important for survival independent of one's earlier history of participation? A nationally representative sample of 457 older persons was followed for 25 years with data from the Level-of-Living Survey and the SWEOLD study. Cox regressions showed that regardless of earlier activities and health, late-life leisure engagement was associated with enhanced survival, especially among men. Among women, earlier activities (study groups) also seem important, perhaps by providing social networks. Results suggest that it is worthwhile to encourage elderly people to participate in leisure activities and to facilitate their participation in the community even at high ages.

  • 33. Agdal, Maren Lillehaug
    et al.
    Raadal, Magne
    Öst, Lars-Göran
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen.
    Skaret, Erik
    Quality-of-life before and after cognitive behavioral therapy (CBT) in patients with intra-oral injection phobia2012Ingår i: Acta Odontologica Scandinavica, ISSN 0001-6357, E-ISSN 1502-3850, Vol. 70, nr 6, s. 463-470Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. To evaluate quality-of-life (QoL), before and after cognitive behavioral therapy (CBT) in patients diagnosed with intra-oral injection phobia according to DSM-IV and to compare with the general population. This study also aimed to evaluate if QoL was associated with self-reported injection anxiety, dental anxiety, time since last dental treatment and oral health. Materials and methods. Subjects were 55 patients (mean age 35.5 +/- 12.2, 78.2% women) who participated in a treatment study in which 89% managed an intra-oral injection at 1 year follow-up. The patients completed a set of questionnaires including Quality of Life Inventory (QOLI), Injection Phobia Scale-Anxiety, Dental Anxiety Scale and a single-item question assessing self-perceived oral health. Objective measures of oral health and treatment needs were based on clinical examination. QOLI-scores from a non-clinical sample were used for comparison. Results. Before treatment the general and health specific QoL were lower among intra-oral injection phobics than in the non-clinical sample. At 1 year follow-up the QoL in general had improved significantly and was similar to that of the non-clinical sample. Poor self-reported oral health and long-term avoidance of dental treatment were associated with lower general and health-specific QoL. Self-reported injection anxiety and dental anxiety were not associated with QoL. Conclusions. Patients with intra-oral injection phobia report lower QoL compared with a general population. Phobia treatment seems to increase QoL to normative levels. Self-perceived poor oral health is associated with reduced QoL in these patients.

  • 34. Agréus, Lars
    et al.
    Hellström, Per M.
    Talley, Nicholas J.
    Wallner, Bengt
    Forsberg, Anna
    Vieth, Michael
    Veits, Lothar
    Björkegren, Karin
    Engstrand, Lars
    Andreasson, Anna
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet. Karolinska Institutet, Sweden.
    Towards a healthy stomach? Helicobacter pylori prevalence has dramatically decreased over 23 years in adults in a Swedish community2016Ingår i: United European Gastroenterology journal, ISSN 2050-6406, E-ISSN 2050-6414, Vol. 4, nr 5, s. 686-696Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background In Western countries the prevalence of Helicobacter pylori (H. pylori) infection may be declining but there is a lack of recent longitudinal population studies. We evaluated the changing epidemiology over a 23-year period in Sweden. Materials and methods In 1989, the validated Abdominal Symptom Questionnaire (ASQ) was mailed to a random sample of inhabitants (ages 22-80 years) in a Swedish community, and 1097 (87%) responded. H. pylori serology was analysed in a representative subsample (n=145). Twenty-three years later, the ASQ was mailed again using similar selection criteria, and 388 out of 1036 responders had an upper endoscopy with assessment of H. pylori and corpus atrophy status. Results The prevalence of positive H. pylori serology decreased from 37.9% (1989) to 15.8% (2012), corresponding to a decrease in odds of 75% per decade (odds ratio (OR): 0.25; 95% confidence interval (CI): 0.11-0.59, p=0.001) independent of age, gender, body mass index (BMI) and level of education, with a pattern consistent with a birth cohort effect. The prevalence increased with increasing age (p=0.001). The prevalence of H. pylori on histology in 2012 was 11.4% (95% CI 8.6-15.0). The prevalence of corpus atrophy on serology and/or histology in 2012 was 3.2% (95% CI 1.8-5.5); all cases were 57 years old. Conclusion The stomach is healthier in 2012 compared with 1989. H. pylori prevalence in adults has decreased over the last two decades to a level where clinical management might be affected.

  • 35.
    Ahacic, Kozma
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för socialt arbete - Socialhögskolan.
    Improvements in the aging population 1968-1991: trends in mobility and dental status2002Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
  • 36. Ahacic, Kozma
    et al.
    Damström-Thakker, Kerstin
    Kåreholt, Ingemar
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Recurring alcohol-related care between 1998 and 2007 among people treated for an alcohol-related disorder in 1997: a register study in Stockholm County2011Ingår i: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 11, s. 574-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Inpatient care for alcohol intoxication is increasing in Sweden, especially among young women. Since it is well known that alcohol disorder is a chronic relapsing illness, this study examines the extent to which people return for more care.

    METHOD: All inpatients with alcohol-related diagnoses in Stockholm County during 1997 were followed prospectively to 2007 through registers. The proportion reappearing for the same diagnosis, other alcohol-related inpatient, or outpatient care each year after baseline, as well as the number of years the inpatients reappeared were calculated (n = 2735). Three diagnoses were examined separately; alcohol dependence, harmful use of alcohol, and alcohol intoxication.

    RESULTS: Three out of five inpatients with an alcohol diagnoses reappeared for more alcohol-related inpatient care during the following decade. The proportion returning was largest the year after baseline and then decreased curvilinearly over time. The inclusion of outpatient care increased proportions, but did not change patterns. Of those with an alcohol dependence diagnosis at baseline 42 percent returned for more alcohol-related inpatient care the first, 28 percent the fifth, and 25 percent the tenth year. Corresponding proportions for harmful use and intoxication were smaller. One in five among those with an alcohol dependence returned for more than five of the ten years. Ordered logistic regressions confirmed that besides diagnosis, age and gender were independently related to the number of years returning to care.

    CONCLUSIONS: While middle-aged males with alcohol dependence were in a revolving door, young female inpatients with intoxication diagnosis returned to a comparably lower degree.

  • 37. Ahacic, Kozma
    et al.
    Kennison, Robert F.
    Kåreholt, Ingemar
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Jönkoping University, Sweden.
    Alcohol abstinence, non-hazardous use and hazardous use a decade after alcohol-related hospitalization: registry data linked to population-based representative postal surveys2014Ingår i: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 14, s. 874-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Although there is evident association between alcohol-related hospitalization and alcohol use, the relationship has not been well examined. This study analyzed the extent of alcohol abstinence, non-hazardous use and hazardous use among people who had experienced alcohol-related hospitalization during the preceding decade. Method: Registry data concerning alcohol-related hospitalizations between 1996 and 2007 were linked to two representative surveys, in 2006 and 2007, of residents of Stockholm County. Relevant contrasts were modeled, using logistic regression, in the pooled sample (n = 54 955). Ages were 23-84 years at follow-up. Results: Among persons previously hospitalized (n = 576), half reported non-hazardous use. Non-hazardous use was less prevalent than in the general population - and the extent of non-hazardous use did not change over time following hospitalization. There were no significant age differences, but non-hazardous use was less frequent among people with repeated episodes of care. One in six was abstinent. Abstinence was more common among the old, while hazardous use (exceeding 14 drinks per week for men, and 9 drinks per week for women) decreased with age. Abstinence also increased over time; among persons hospitalized ten years ago, the abstinence rate was twice that of the general population. Associations with hazardous use over time were less conclusive. Hazardous use among those previously hospitalized decreased over time in one sample but not in the other. After pooling the data, there were indications of a decrease over time following hospitalization, but more prevalent hazardous use than in the general population. Conclusions: Following alcohol-related hospitalization, abstinence increased, and there was no evidence of regression towards the mean, i.e., towards non-hazardous use. Abstinence was also more widespread among previously hospitalized persons of older ages. With advancing age, changing hazardous alcohol habits among previously hospitalized appears to yield a trend towards promotion of abstinence.

  • 38. Ahacic, Kozma
    et al.
    Kennison, Robert F.
    Kåreholt, Ingemar
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Changes in sobriety in the Swedish population over three decades: age, period or cohort effects?2012Ingår i: Addiction, ISSN 0965-2140, E-ISSN 1360-0443, Vol. 107, nr 4, s. 748-755Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims  This study aimed to examine age, cohort and period trends in alcohol abstinence.

    Design  Two surveys, the Level of Living Survey collected in 1968, 1974, 1981, 1990 and 2000, and the Swedish Panel Study of the Oldest Old (SWEOLD) collected in 1992 and 2002, were studied with graphical depictions of cross-sectional and longitudinal data presented over time and over age. Cross-sectional 10-year age group differences, time-lag differences between waves and within-cohort differences between waves for 10-year birth cohorts were examined. Logistic regression models were applied to confirm the observed patterns.

    Setting  The samples were representative of the Swedish population.

    Participants  Participants ranged in age from 18 to 75 (n = 5000 per wave), and 77+ at later waves (n = 500).

    Measurements  Alcohol abstinence was determined by asking ‘Do you ever drink wine, beer, or spirits?’, where a ‘no’ response indicated abstinence.

    Findings  Decreases in abstinence rates were observed from 1968 to 2000/02. While cross-sectional analysis indicated increased abstinence with advancing age, the longitudinal analysis suggested otherwise. Inspection of cohort differences revealed little change within cohorts and large differences between cohorts; abstinence rates declined in later-born cohorts up to the 1940s birth cohorts; stability was observed in cohorts born since the 1940s. Logistic regression models indicated that neither age nor period were significant (P > 0.05) predictors of abstinence when cohort (P < 0.001) was included.

    Conclusion  Decreasing proportions of total alcohol abstainers in Sweden from 1968 to 2000 appear to be attributable primarily to decreases in successive cohorts rather than drinkers becoming abstainers.

  • 39. Ahacic, Kozma
    et al.
    Kåreholt, Ingemar
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Karolinska Institute .
    Helgason, Asgeir R.
    Allebeck, Peter
    Non-response bias and hazardous alcohol use in relation to previous alcohol-related hospitalization: comparing survey responses with population data2013Ingår i: Substance Abuse Treatment, Prevention, and Policy, ISSN 1747-597X, E-ISSN 1747-597X, Vol. 8, s. 10-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: This study examines whether alcohol-related hospitalization predicts survey non-response, and evaluates whether this missing data result in biased estimates of the prevalence of hazardous alcohol use and abstinence. Methods: Registry data on alcohol-related hospitalizations during the preceding ten years were linked to two representative surveys. Population data corresponding to the surveys were derived from the Stockholm County registry. The alcohol-related hospitalization rates for survey responders were compared with the population data, and corresponding rates for non-responders were based on the differences between the two estimates. The proportions with hazardous alcohol use and abstinence were calculated separately for previously hospitalized and non-hospitalized responders, and non-responders were assumed to be similar to responders in this respect. Results: Persons with previous alcohol-related admissions were more likely currently to abstain from alcohol (RR=1.58, p<.001) or to have hazardous alcohol use (RR=2.06, p<.001). Alternatively, they were more than twice as likely to have become non-responders. Adjusting for this skewed non-response, i. e., the underrepresentation of hazardous users and abstainers among the hospitalized, made little difference to the estimated rates of hazardous use and abstinence in total. During the ten-year period 1.7% of the population were hospitalized. Conclusions: Few people receive alcohol-related hospital care and it remains unclear whether this group's underrepresentation in surveys is generalizable to other groups, such as hazardous users. While people with severe alcohol problems - i.e. a history of alcohol-related hospitalizations -are less likely to respond to population surveys, this particular bias is not likely to alter prevalence estimates of hazardous use.

  • 40.
    Ahacic, Kozma
    et al.
    Karolinska institutet.
    Trygged, Sven
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för socialt arbete - Socialhögskolan.
    Kåreholt, Ingemar
    Ageing Research Centre, SU och KI.
    Income and education as predictors of stroke mortality after the survival of a first stroke2012Ingår i: Stroke Research and Treatment, ISSN 2090-8105, E-ISSN 2042-0056, Vol. 2012, s. 1-6Artikel i tidskrift (Refereegranskat)
  • 41. Ahlberg, Mia
    et al.
    Ekéus, Cecilia
    Hjern, Anders
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om ojämlikhet i hälsa (CHESS).
    Birth by vacuum extraction delivery and school performance at 16 years of age2013Ingår i: American Journal of Obstetrics and Gynecology, ISSN 0002-9378, E-ISSN 1097-6868, Vol. 210, nr 4, s. 361.e1-361.8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective 

    The aim of the present study was to investigate cognitive competence, as indicated by school performance, at 16 years of age, in children delivered by vacuum extraction.

    Study design 

    This was a register study of a national cohort of 126,032 16 year olds born as singletons, with a vertex presentation, at a gestational age of 34 weeks or older, with Swedish-born parents, delivered between 1990 and 1993 without major congenital malformations. Linear regression was used to analyze mode of delivery in relation to mean scores from national tests in mathematics (40.2; scale, 10-75; SD, 14.9) and mean average grades (223.8; scale, 10-320; SD, 52.3), with adjustment for perinatal and sociodemographic confounders.

    Results

    Children delivered by vacuum extraction (-0.51; 95% confidence interval [CI], -0.76 to 0.26) as well as by nonplanned cesarean section (-0.51; 95% CI, -0.82 to -0.20) had slightly lower mean mathematics test scores than children born vaginally without instruments, after adjustment for major confounders. Mean average grades in children delivered by vacuum extraction were -1.05 (95% CI, -1.87 to -0.23) and -1.20 (95% CI,-2.24 to -0.16) in children delivered by nonplanned cesarean section compared with children born vaginally.

    Conclusion

    Children delivered by vacuum extraction had slightly lower grades at age 16 years compared with those born by noninstrumental vaginal delivery but very similar to those delivered by nonplanned cesarean. This suggests that vacuum extraction and nonplanned cesarean are equivalent alternatives for terminating deliveries with respect to cognitive outcomes.

  • 42.
    Ahlbom, Anders
    et al.
    Karolinska Institutet.
    Drefahl, Sven
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Sociologiska institutionen.
    Lundström, Hans
    Statistics Sweden.
    Den åldrande befolkningen2010Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 107, nr 48, s. 3048-3051Artikel i tidskrift (Refereegranskat)
  • 43. Ahlsson, Fredrik
    et al.
    Kaijser, Magnus
    Adami, Johanna
    Lundgren, Maria
    Palme, Mårten
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Nationalekonomiska institutionen.
    School Performance After Preterm Birth2015Ingår i: Epidemiology, ISSN 1044-3983, Vol. 26, nr 1, s. 106-111Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: An increased risk of poor school performance for children born preterm has been shown in many studies, but whether this increase is attributable to preterm birth per se or to other factors associated with preterm birth has not been resolved. Methods: We used data from the Swedish Medical Birth Register, the Longitudinal Integration Database for Sickness Insurance and Labor Market Study, the Swedish Multigeneration Register, and the National School Register to link records comprising the Swedish birth cohorts from 1974 through 1991. Linear regression was used to assess the association between gestational duration and school performance, both with and without controlling for parental and socioeconomic factors. In a restricted analysis, we compared siblings only with each other. Results: Preterm birth was strongly and negatively correlated with school performance. The distribution of school grades for children born at 31-33 weeks was on average 3.85 (95% confidence interval = -4.36 to -3.35) centiles lower than for children born at 40 weeks. For births at 22-24 weeks, the corresponding figure was -23.15 (-30.32 to -15.97). When taking confounders into account, the association remained. When restricting the analysis to siblings, however, the association between school performance and preterm birth after week 30 vanished completely, whereas it remained, less pronounced, for preterm birth before 30 weeks of gestation. Conclusions: Our study suggests that the association between school performance and preterm birth after 30 gestational weeks is attributable to factors other than preterm birth per se.

  • 44. Ahlstrand, Tuuli
    et al.
    Torittu, Annamari
    Elovaara, Heli
    Välimaa, Hannamari
    Pöllänen, Marja T.
    Kasvandik, Sergo
    Högbom, Martin
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Ihalin, Riikka
    Interactions between the Aggregatibacter actinomycetemcomitans secretin HofQ and host cytokines indicate a link between natural competence and interleukin-8 uptake2018Ingår i: Virulence, ISSN 2150-5594, E-ISSN 2150-5608, Vol. 9, nr 1, s. 1205-1223Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Naturally competent bacteria acquire DNA from their surroundings to survive in nutrient-poor environments and incorporate DNA into their genomes as new genes for improved survival. The secretin HofQ from the oral pathogen Aggregatibacter actinomycetemcomitans has been associated with DNA uptake. Cytokine sequestering is a potential virulence mechanism in various bacteria and may modulate both host defense and bacterial physiology. The objective of this study was to elucidate a possible connection between natural competence and cytokine uptake in A. actinomycetemcomitans. The extramembranous domain of HofQ (emHofQ) was shown to interact with various cytokines, of which IL-8 exhibited the strongest interaction. The dissociation constant between emHofQ and IL-8 was 43nM in static settings and 2.4M in dynamic settings. The moderate binding affinity is consistent with the hypothesis that emHofQ recognizes cytokines before transporting them into the cells. The interaction site was identified via crosslinking and mutational analysis. By structural comparison, relateda type I KH domain with a similar interaction site was detected in the Neisseria meningitidis secretin PilQ, which has been shown to participate in IL-8 uptake. Deletion of hofQ from the A. actinomycetemcomitans genome decreased the overall biofilm formation of this organism, abolished the response to cytokines, i.e., decreased eDNA levels in the presence of cytokines, and increased the susceptibility of the biofilm to tested -lactams. Moreover, we showed that recombinant IL-8 interacted with DNA. These results can be used in further studies on the specific role of cytokine uptake in bacterial virulence without interfering with natural-competence-related DNA uptake.

  • 45. Ahlström, Christer
    et al.
    Anund, Anna
    Fors, Carina
    Åkerstedt, Torbjörn
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet. Karolinska Institute, Sweden.
    Effects of the road environment on the development of driver sleepiness in young male drivers2018Ingår i: Accident Analysis and Prevention, ISSN 0001-4575, E-ISSN 1879-2057, Vol. 112, s. 127-134Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Latent driver sleepiness may in some cases be masked by for example social interaction, stress and physical activity. This short-term modulation of sleepiness may also result from environmental factors, such as when driving in stimulating environments. The aim of this study is to compare two road environments and investigate how they affect driver sleepiness. Thirty young male drivers participated in a driving simulator experiment where they drove two scenarios: a rural environment with winding roads and low traffic density, and a suburban road with higher traffic density and a more built-up roadside environment. The driving task was essentially the same in both scenarios, i.e. to stay on the road, without much interaction with other road users. A 2 x 2 design, with the conditions rural versus suburban, and daytime (full sleep) versus night-time (sleep deprived), was used. The results show that there were only minor effects of the road environment on subjective and physiological indicators of sleepiness. In contrast, there was an increase in subjective sleepiness, longer blink durations and increased EEG alpha content, both due to time on task and to night-time driving. The two road environments differed both in terms of the demand on driver action and of visual load, and the results indicate that action demand is the more important of the two factors. The notion that driver fatigue should be countered in a more stimulating visual environment such as in the city is thus more likely due to increased task demand rather than to a richer visual scenery. This should be investigated in further studies.

  • 46. Ahlström, Christer
    et al.
    Fors, Carina
    Anund, Anna
    Hallvig, David
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet.
    Video-based observer rated sleepiness versus self-reported subjective sleepiness in real road driving2015Ingår i: European Transport Research Review, ISSN 1867-0717, E-ISSN 1866-8887, Vol. 7, nr 4, artikel-id 38Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: Observer-rated sleepiness (ORS) based on video recordings of the driver's face is often used when analysing naturalistic driving data. The aim of this study is to investigate if ORS ratings agree with subjective self-reported sleepiness (SRS). Methods: Forty raters assessed 54 video-clips showing drivers with varying levels of sleepiness. The video-clips were recorded during a field experiment focusing on driver sleepiness using the same cameras that are typically used in large-scale field studies. The weak results prompted a second test. Ten human factors researchers made pairwise comparisons of videos showing the same four participants in an alert versus a very sleepy condition. The task was simply to select the video-clip where the driver was sleepy. Results: The overall average percentage of video segments where ORS and SRS matched was 41 % in Test 1. ORS 0 (alert) and ORS 2 (very sleepy) were easier to score than ORS 1 and it was slightly harder to rate night-time drives. Inter-rater agreement was low, with average Pearson's r correlations of 0.19 and Krippendorff's alpha of 0.15. In Test 2, the average Pearson's r correlations was 0.35 and Krippendorff's alpha was 0.62. The correspondence between ORS and SRS showed an agreement of 35 %. Conclusions: The results indicate that ORS ratings based on real road video recordings correspond poorly with SRS and have low inter-rater agreement. Further research is necessary in order to further evaluate the usefulness of ORS as a measure of sleepiness.

  • 47. Ahlström, Christer
    et al.
    Nyström, Marcus
    Holmqvist, Kenneth
    Fors, Carina
    Sandberg, David
    Anund, Anna
    Kecklund, Göran
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet.
    Åkerstedt, Torbjörn
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet.
    Fit-for-duty test for estimation of drivers' sleepiness level: Eye movements improve the sleep/wake predictor2013Ingår i: Transportation Research Part C: Emerging Technologies, ISSN 0968-090X, E-ISSN 1879-2359, Vol. 26, s. 20-32Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Driver sleepiness contributes to a considerable proportion of road accidents, and a fit-for-duty test able to measure a driver’s sleepiness level might improve traffic safety. The aim of this study was to develop a fit-for-duty test based on eye movement measurements and on the sleep/wake predictor model (SWP, which predicts the sleepiness level) and evaluate the ability to predict severe sleepiness during real road driving. Twenty-four drivers participated in an experimental study which took place partly in the laboratory, where the fit-for-duty data were acquired, and partly on the road, where the drivers sleepiness was assessed. A series of four measurements were conducted over a 24-h period during different stages of sleepiness. Two separate analyses were performed; a variance analysis and a feature selection followed by classification analysis. In the first analysis it was found that the SWP and several eye movement features involving anti-saccades, pro-saccades, smooth pursuit, pupillometry and fixation stability varied significantly with different stages of sleep deprivation. In the second analysis, a feature set was determined based on floating forward selection. The correlation coefficient between a linear combination of the acquired features and subjective sleepiness (Karolinska sleepiness scale, KSS) was found to be R = 0.73 and the correct classification rate of drivers who reached high levels of sleepiness (KSS ⩾ 8) in the subsequent driving session was 82.4% (sensitivity = 80.0%, specificity = 84.2% and AUC = 0.86). Future improvements of a fit-for-duty test should focus on how to account for individual differences and situational/contextual factors in the test, and whether it is possible to maintain high sensitive/specificity with a shorter test that can be used in a real-life environment, e.g. on professional drivers.

  • 48. Aho, Vilma
    et al.
    Ollila, Hanna M.
    Rantanen, Ville
    Kronholm, Erkki
    Surakka, Ida
    van Leeuwen, Wessel M. A.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet. University of Helsinki, Finland; Finnish Institute of Occupational Health, Finland.
    Lehto, Maili
    Matikainen, Sampsa
    Ripatti, Samuli
    Härmä, Mikko
    Sallinen, Mikael
    Salomaa, Veikko
    Jauhiainen, Matti
    Alenius, Harri
    Paunio, Tiina
    Porkka-Heiskanen, Tarja
    Partial Sleep Restriction Activates Immune Response-Related Gene Expression Pathways: Experimental and Epidemiological Studies in Humans2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 10, artikel-id e77184Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Epidemiological studies have shown that short or insufficient sleep is associated with increased risk for metabolic diseases and mortality. To elucidate mechanisms behind this connection, we aimed to identify genes and pathways affected by experimentally induced, partial sleep restriction and to verify their connection to insufficient sleep at population level. The experimental design simulated sleep restriction during a working week: sleep of healthy men (N = 9) was restricted to 4 h/night for five nights. The control subjects (N = 4) spent 8 h/night in bed. Leukocyte RNA expression was analyzed at baseline, after sleep restriction, and after recovery using whole genome microarrays complemented with pathway and transcription factor analysis. Expression levels of the ten most up-regulated and ten most down-regulated transcripts were correlated with subjective assessment of insufficient sleep in a population cohort (N = 472). Experimental sleep restriction altered the expression of 117 genes. Eight of the 25 most up-regulated transcripts were related to immune function. Accordingly, fifteen of the 25 most up-regulated Gene Ontology pathways were also related to immune function, including those for B cell activation, interleukin 8 production, and NF-kappa B signaling (P<0.005). Of the ten most up-regulated genes, expression of STX16 correlated negatively with self-reported insufficient sleep in a population sample, while three other genes showed tendency for positive correlation. Of the ten most down-regulated genes, TBX21 and LGR6 correlated negatively and TGFBR3 positively with insufficient sleep. Partial sleep restriction affects the regulation of signaling pathways related to the immune system. Some of these changes appear to be long-lasting and may at least partly explain how prolonged sleep restriction can contribute to inflammation-associated pathological states, such as cardiometabolic diseases.

  • 49.
    Ahrén, Jennie
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om ojämlikhet i hälsa (CHESS).
    Barn till överskuldsatta: underlagsrapport till Barns och ungas hälsa, vård och omsorg 20132013Rapport (Övrigt vetenskapligt)
  • 50.
    Ahrén, Jennie C.
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om ojämlikhet i hälsa (CHESS).
    Chiesa, F.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om ojämlikhet i hälsa (CHESS).
    Koupil, Ilona
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om ojämlikhet i hälsa (CHESS).
    Magnusson, C.
    Goodman, A.
    We are family - parents, siblings and eating disorders: Introducing the Stockholm Youth Cohort2012Ingår i: European psychiatry, ISSN 0924-9338, E-ISSN 1778-3585, Vol. 27, nr 1, s. P-251-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Eating disorders (ED) are among the leading causes of disease burden, especially in women.

    Objectives: The overall aim is to explore role of parental social characteristics and family composition in the development of ED in adolescent males and females.

    Aims: We investigated associations of parental socioeconomic position, family type, number of siblings and half-siblings and history of psychiatric disease in parents with the incidence of eating disorders at age 12–23 years.

    Methods: The Stockholm Youth Cohort (N = 589,114) is a database created by record-linkage for all children and adolescents, 0–17 years, resident in Stockholm County during the period 2001–2007, their parents and siblings. Hazard rations were calculated using Cox regression. Cases of ED were identified in outpatient care.

    Results: A total of 3251 cases of ED (2971 females and 280 males) were recorded among 249,884 study subjects. There was an increased risk of ED in both male and female offspring of parents who had a history of alcohol and drug abuse or psychiatric ill-health. Higher parental education was a risk factors in females. Increasing number of full siblings had a protective effect (fully adjusted HR 0.91, 95% CI 0.87–0.96, per sibling) while increasing number of half-siblings appeared to increase risk of eating disorders in females.

    Conclusions: Risk factors for ED seem to differ between females and males. While parental psychiatric health is related to risk of ED in both sexes, family socioeconomic position and relationships within family appear to be of more importance for influencing risk of ED in females.

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