Publikationer 2014 – Københavns Universitet

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 Publications 2014

The list of publications by scientists from Center for Healthy Aging is only in English as most publications are published in English.

Listen over videnskabelige publikationer af forskere fra Center for Sund Aldring er kun på engelsk, da de fleste publikationer kun bliver offentliggjort på engelsk.

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Measuring risk, managing values: health technology and subjectivity in Denmark. Andersen JH, Whyte SR. Anthropology & Medicine. DOI:10.1080/13648470.2014.907022, 2014.

Based on fieldwork among Danes with a diagnosed risk of type 2 diabetes or cardiovascular disease, this paper investigates how the technological possibilities of diagnosing and monitoring invisible risks shape understandings of health and form subjectivity. It focuses on the experiences of being diagnosed with a risk condition in the form of high blood pressure or elevated blood glucose and the ensuing use of measuring devices. It argues that measurements of these conditions can be seen as 'formative processes' that produce and maintain a view of health as something that can best be known through the use of medical technology. The numerical values such measurements yield are seen as true indicators of health, and doing something about risk conditions is felt to be a personal imperative. The formative processes illustrated in this paper are motivational and thought provoking...

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Providing rehabilitation online – invisible work and diagnostic agents. Bødker M, Nielsen AJ. Journal of Health Organization and Management.

Purpose: Telecare promises to deliver healthcare services more efficiently while, at the same time, improving the quality of care. This paper challenges these promises by analysing the implications of introducing telecare in the rehabilitation of COPD patients. Design/methodology/approach: Empirically, the paper is based on interviews with and observations of rehabilitation therapists and patients taking part in a Danish telerehabilitation programme. Theoretically, the paper draws on Science and Technology Studies. Findings: The introduction of telecare alters rehabilitation practices in multiple ways. First, several new time-consuming work routines, carried out in a collaboration of therapists, patients and technical professions, emerge. Although crucial in establishing and maintaining telerehabilitation infrastructures, this work remains invisible in evaluations of the programme. Second, rather than simply increasing patient agency, responsibilities are redistributed and negotiated in subtle and non-uniform ways.

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Hurrah for the increasing longevity: feasible strategies to counteract age-related loss of skeletal muscle mass. Holm L, Jespersen A, Nielsen DS, Frøst MB, Reitelseder S, Jensen T, Engelsen SB, Kjaer M, Damsholt T. Scand J Med Sci Sports.

Antidepressant therapy after hospitalization with depression: Non-Western immigrants compared with Danish-born residents. Kildemoes HW, Thomsen LT, Kriegbaum M, Petersen JH, Nørredam ML. BMC Psychiatry. Mar 17;14(1):77, 2014.

Antidepressant (AD) therapy is recommended for patients 4-12 months after remission from depression. The aim was to examine whether immigrants (refugees or family reunited immigrants) from non-Western countries are at greater risk than Danish-born residents of 1) not initiating AD therapy after discharge and 2) early AD discontinuation.

A cohort of immigrants from non-Western countries (n = 132) and matched Danish-born residents (n = 396) discharged after first admission with moderate to severe depression between 1 January 1996 and 31 May 2008 was followed in the Danish registries.Logistic regression models were applied to explore AD initiation within 30 days after discharge, estimating odds ratio (OR) for immigrants versus Danish-born residents.Early discontinuation was explored by logistic regression, estimating OR for no AD dispensing within 180 days after the first dispensing, and by Cox regression, estimating hazard ratio (HR) for discontinuation (maximum drug supply gap) within 180 days.

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Do Social background and intelligence early in life  influence use of coronary heart disease preventive medicine in adulthood? Kriegbaum M, Kildemoes HW, Rasmussen JN, Hendriksen C, Vass M, Mortensen EL, Osler M. BMJ Open. Jan 17;4 (1), 2014.

Billiards, rhythms, collectives - Billiards at a Danish activity centre as a culturally specific form of active ageing. Lassen AJ. Ethnologia Europaea 44:1: 57-74, 2014.

Keeping disease at arm's length: How older Danish people distance disease through active ageing. Lassen AJ. Ageing & Society. First view article, 2014.

Many older people live with a range of chronic diseases. However, these diseases do not necessarily impede an active lifestyle. In this article the author analyses the relation between the active ageing discourse and the way older people at two Danish activity centres handle disease. How does active ageing change everyday life with chronic disease, and how do older people combine an active life with a range of chronic diseases? The participants in the study use activities to keep their diseases at arm's length, and this distancing of disease at the same time enables them to engage in social and physical activities at the activity centre. In this way, keeping disease at arm's length is analysed as an ambiguous health strategy. The article shows the importance of looking into how active ageing is practised, as active ageing seems to work well in the everyday life of the older people by not giving emphasis to disease. The article is based on ethnographic fieldwork and uses vignettes of four participants to show how they each keep diseases at arm's length.

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Unmaking old age - political and cognitive formats of active ageing. Lassen AJ, Moreira T. Journal og Aging Studies. 30:1 33-46, 2014.

Active ageing is a policy tool that dominates the way the ageing society has been constituted during the last decades. The authors argue that active ageing is an attempt at unmaking the concept of old age, by engaging in the plasticity of ageing in various ways. Through a document study of the different epistemes, models and forms used in the constitution of active ageing policies, the authors show how active ageing is not one coordinated set of policy instruments, but comes in different formats. In the WHO, active ageing configures individual lifestyle in order to expand the plasticity of ageing, based on epidemiological and public health conventions. In the EU, active ageing reforms the retirement behaviour of populations in order to integrate the plasticity of ageing into the institutions, based on social gerontological and demographic conventions. 

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Innovating for 'active ageing' in public-private innovation partnership: creating doable problems and alignment. Lassen AJ, Bønnelycke J, Otto L. Technological Forecasting & Social Change. First view article, 2014.

By focusing on different constructions of the elderly and how these definitions are aligned within a Danish public–private innovation partnership called No Age, the article examines how various understandings of ‘the elderly’, ‘active ageing’ and ‘health’ clash and entangle in innovation work. The ambition of No Age is to create welfare technologies for elderly people. The authors were invited to contribute ethnographic insights to the partnership. We argue that the No Age's innovation process creates doable problems by co-producing technological solutions, their users and the health issues the products are designed to address. Furthermore, we argue that the specific constellation and alignment of actors in such a partnership define how and what kinds of users are constituted, as the target groups and success criteria for the development of welfare technologies are shaped throughout the innovation process rather than decided at the beginning. This has implications for the role of ethnographers as providers of user-insights in health-related innovation projects.

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Tværfaglighed som ideal og praksis – folkesundhedsvidenskabelige erfaringer i at uddanne på tværs af faggrænser. Nielsen AJ, Vallgårda S. Danmarks Universitetspædagogiske Tidsskrift. 9 (16): 113-123, 2014.

Uddannelsespolitisk fokuseres der i stigende grad på tværfaglighed. Nye uddannelser, som kombinerer flere discipliner, etableres, og tværfaglighed er ofte et kriterium for finansiering af forskningsprojekter. Tværfaglighed associeres af mange med attraktive egenskaber og muligheder som skræddersyede studieforløb, flerstrengede kompetenceprofiler, det bedste fra forskellige discipliner, ny innovativ viden m. m. Men kan tværfaglighed virkelig høste det bedste fra alle verdner? Og hvad indebærer tværfaglighed egentlig? 

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En sund ældrepædagogik?. Nørtoft K. Vera Tidsskrift for pædagoger. Accepted, 2014. 

Measuring and Managing Bodies in the Later Life Course. Oxlund B, Whyte SR. Journal of Population Ageing. Vol. 7, Nr. 3, 217-230, 2014.

Health care agreements as a tool for coordinating health and social services. Rudkjøbing A, Strandberg-Larsen M, Vrangbaek K, Andersen JS, Krasnik A. International Journal of Integrated Care. (Exp. publication December 2014), Accepted.

Introduction:

In 2007, a substantial reform changed the administrative boundaries of the Danish health care system and introduced health care agreements to be signed between municipal and regional authorities. To assess the health care agreements as a tool for coordinating health and social services, a survey was conducted before (2005-2006) and after the reform (2011). The study was designed on the basis of a modified version of Alter and Hage's framework for conceptualising coordination. Both surveys addressed all municipal level units (n = 271/98) and a random sample of general practitioners (n = 700/853).

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Evaluation of a policy to strenthen case management and quality of diabetes care in Generel Practice in Denmark. Rudkjøbing A, Vrangbaek K, Birk HO, Andersen JS, Krasnik A.

Objectives:

To evaluate the utilization of a policy for strengthening general practitioner's case management and quality of care of diabetes patients in Denmark incentivized by a novel payment mode. We also want to elucidate any geographical variation or variation on the basis of practice features such as solo- or group practice, size of practice and age of the GP. On the basis registers encompassing reimbursement data from GPs and practice specific information about geographical location (region), type of practice (solo- or group-practice), size of practice (number of patients listed) and age of the GP were are able to determine differences in use of the policy in relation to the practice-specific information.

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The challenges of human population ageing. Sander M, Oxlund B, Jespersen A, Krasnik A, Mortensen EL, Westendorp RGJ, Rasmussen LJ. Age and Ageing. Vol. 0, 1-3, 2014.

The 20th century saw an unprecedented increase in average human lifespan as well as a rapid decline in human fertility in many countries of the world. The accompanying worldwide change in demographics of human populations is linked to unanticipated and unprecedented economic, cultural, medical, social, public health and public policy challenges, whose full implications on a societal level are only just beginning to be fully appreciated.

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Physician-industry collaboration: conflicts of interest and the imputation of motive. Wadmann S. Social Studies of Science. 44(4):531-554, 2014.

Policies about physicians' involvement with pharmaceutical companies spawn contradictory ideas. One set of policies aims to stimulate collaboration between private companies and publicly employed researchers to spur innovation and economic growth, another addresses what is seen as the problem of physicians' conflicts of interest stemming from industry collaboration. This article explores how these contradictory policies interact with everyday practice in clinical hypertension research in Denmark. I argue that 'corporate' and 'academic' research is entangled as physicians participate in industry trials to pursue their own research. Building on document analysis, observations of contract research, and interviews with clinician researchers and industry executives, I show how the establishment of industry 'ties' can serve as a way for physicians to navigate the constraints of research infrastructures and live up to intergenerational norms that knit the medical collective together.

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Beyond the therapeutic misconception: Research, care and moral friction. Biosocieties. Wadmann S., Hoeyer K. 9: 3-23, 2014.

In research ethics regulation, health care and research are depicted as serving distinct goals, and policies are in place to prevent what is seen as patients’ misconceived understanding of research as health care. On the basis of ethnographic research in four Danish hospitals in conjunction with a cardiovascular drug trial in patients with chronic disease, we argue that the objectives of health care and research often merge in mutually constitutive practices. We build on observations of trial activities, interviews with physician-investigators, research nurses, patient-participants and trial sponsors and a survey of the patient-participants. We found an organization of clinical drug trials allowing extraordinary care relationships to form, which makes trial participation attractive for patients and allows information to flow more freely. 

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Theme 2Til toppen

Cognitive development over 8 years in midlife and its association with cardiovascular risk factors. Anstey KJ, Sargent-Cox K, Garde E, Cherbuin N, Butterworth P. Neuropsychology. 28:653-65, 2014.

Abstract:

We describe population-level cognitive development in early middle-age and evaluate whether cardiovascular risk factors for late-onset dementia influence cognitive change in midlife. The sample from the PATH Through Life (PATH) Project (N = 2,530; 40-44 years of age at baseline) was drawn randomly from the community, followed for 8 years, and assessed on cognitive function, health, and lifestyle risk factors at 4 yearly intervals. A summary risk score (PATHrisk) was computed for presence of smoking, hypertension, depression, high body mass index, diabetes, and insufficient physical activity.

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Copenhagen Aging and Midlife Biobank (CAMB): An introduction. Avlund K, Osler M, Mortensen EL, Christensen U, Bruunsgaard H, Holm-Pedersen P, Fiehn N-E, Hansen ÅM, Bachkati SH, Meincke RH, Jepsen E, Molbo D., Lund R. Journal of Aging and Health. 26: 5-20, 2014.

Fertility treatment and child intelligence, attention, and executive functions in 5-year-old singletons: a cohort study. Bay B, Mortensen EL, Kesmodel U. BJOG.121: 1642-1651, 2014.

Abstract:

To assess the association of fertility treatment and subfertility with offspring intelligence, attention, and executive functions in 5-year-old singletons. Follow-up study. A cohort of 1782 children sampled from the Danish National Birth Cohort. The children were tested with a neuropsychological battery at age five. In addition to tests of intelligence, attention and executive functions, the follow up included extensive information on important covariates. The analyses were conducted using multiple linear regression and adjusted for parental educational level, maternal intelligence, age, parity, body mass index, smoking in pregnancy, alcohol consumption in pregnancy and child gender, child age, and examiner.

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Significant gender difference in serum levels of fibroblast growth factor 21 in Danish Children and adolescents. Bisgaard A, Sørensen K, Johannsen TH, Helge JW, Andersson AM, Juul A. Int J Pediatr Endocrinol. 7, 2014.

Abstract:

Fibroblast Growth Factor 21 (FGF21) is a novel metabolic factor with effect on glucose and lipid metabolism, and shown to be elevated in diseases related to metabolic syndrome. Due to the increasing frequency of metabolic syndrome in the pediatric population, and as FGF21 studies in children are limited, we investigated baseline serum levels of FGF21 in healthy children during an oral glucose tolerance test. A total of 179 children and adolescents from the COPENHAGEN Puberty Study were included. An OGTT with glucose and insulin measurements, a dual energy X-ray absorptiometry (DXA) scan and a clinical examination including pubertal staging were done on all subjects. Serum levels of FGF21, adiponectin, and leptin were determined by immunoassays at baseline.

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Effects of body size and change in body size from infancy through childhood on body mass index in adulthood. Bjerregaard LG, Rasmussen KM, Michaelsen KF, Skytthe A, Mortensen EL, Baker JL, Sørensen TIA. International Journal of Obesity. 38: 1305-1311, 2014.

Abstract

Weight and weight gain throughout infancy are related to later obesity, but whether the strength of the associations varies during the infancy period is uncertain. Our aims were to identify the period of infancy when change in body weight has the strongest association with adult body mass index (BMI) and also the extent to which these associations during infancy are mediated through childhood BMI. The Copenhagen Perinatal Cohort, in which participants were followed from birth through 42 years of age, provided information on weight at 12 months and BMI at 42 years for 1633 individuals. Information on weight at birth, 2 weeks, 1, 2, 3, 4 and 6 months was retrieved from health visitors' records and information on BMI at ages 7 and 13 years from school health records. The associations of infant weight and weight gain standard deviation scores (SDS) with adult BMI-SDS were analyzed using multiple linear regression and path analysis.

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Reliability and Hierarchical Structure of DSM-5 Pathological Traits in a Danish Mixed Sample. Bo S, Bach B, Mortensen EL, Simonsen E. Journal of Personality Disorders. Accepted, 2014.

Abstract:

In this study we assessed the DSM-5 trait model in a large Danish sample (n = 1,119) with respect to reliability of the applied Danish version of the Personality Inventory for DSM-5 (PID-5) self-report form by means of internal consistency and item discrimination. In addition, we tested whether the five-factor structure of the DSM-5 trait model can be replicated in a Danish independent sample using the PID-5 self-report form. Finally, we examined the hierarchical structure of DSM-5 traits. In terms of internal consistency and item discrimination, the applied PID-5 scales were generally found reliable and functional; our data resembled the five-factor structure of previous findings, and we identified a hierarchical structure from one to five factors that was conceptually reasonable and corresponded with existing findings. These results support the new DSM-5 trait model and suggest that it can be generalized to other languages and cultures.

Cohort Profile: The Danish Conscription Database (DCD): A cohort of 728 160 men born from 1939 through 1959. Christensen GT, Molbo D, Angquist LH, Mortensen EL, Christensen K, Sorensen TI, Osler M. International journal of epidemiology. Accepted, 2014.

Abstract:

The Danish Conscription Database (DCD) was established to enable studies of the influence of early physical and mental exposures on adverse health and social outcomes from a life-course perspective. In Denmark, all young men are requested to appear before the conscription board when they turn 18 years, to be assessed for military service. The DCD was established by digitizing information from conscription board register cards on the height, weight, educational level, intelligence test score and examination details of Danish conscripts. The DCD contains information on 728,160 men born from 1939 through 1959 and examined by the conscription board from 1957 through 1984. The unique Danish personal identification number of each individual conscript has been traced, and this allows linkage of the DCD to all Danish health and socioeconomic registers. More than 130,000 deaths have been identified in a recent linkage to the Danish Register of Cause of Death. We encourage collaboration, and interested researchers should contact: danishconscriptiondatabase.glostrup-hospital@regionh.dk.

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Addressing social inequality in aging by the Danish Occupational Social Class Measurement. Christensen U, Krølner R, Nilsson CJ, Lyngbye PW, Hougaard CØ, Nygaard E, Thielen K, Avlund K, Holstein BE, Lund R. Journal of Aging and Health. 26:106-27, 2014.

Abstract:

To present the Danish Occupational Social Class (DOSC) measurement as a measure of socioeconomic position (SEP) applicable in a late midlife population, and to analyze associations of this measure with three aging-related outcomes in midlife, adjusting for education. Systematic coding procedures of the DOSC measurement were applied to 7,084 participants from the Copenhagen Aging and Midlife Biobank (CAMB) survey. We examined the association of this measure of SEP with chronic conditions, self-rated health, and mobility in logistic regression analyses, adjusting for school education in the final analysis.

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Impaired sleep and allostatic load: cross sectional results from the Danish Copenhagen Aging and Midlife Biobank. Clark AJ, Dich N, Lange T, Jennum P, Hansen AM, Lund R, Rod NH. Sleep Med. 15: 1571-1578, 2014.

Abstract:

Understanding the mechanisms linking sleep impairment to morbidity and mortality is important for future prevention, but these mechanisms are far from elucidated. We aimed to determine the relation between impaired sleep, both in terms of duration and disturbed sleep, and allostatic load (AL), which is a measure of systemic wear and tear of multiple body systems, as well as with individual risk markers within the cardiac, metabolic, anthropometric, and immune system. A cross-sectional population-based study of 5226 men and women from the Danish Copenhagen Aging and Midlife Biobank with comprehensive information on sleep duration, disturbed sleep, objective measures of an extensive range of biological risk markers, and physical conditions.

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Early life adversity potentiates the effects of later life stress on cumulative physiological dysregulation. Dich N, Hansen AM, Avlund K, Lund R, Mortensen EL, Bruunsgaard H, Rod NH. Anxiety, Stress and Coping. 30: Accepted, 2014.

Abstract:

Previous research indicates that early life adversity may heighten stress reactivity and impair mechanisms for adaptive coping, suggesting that experience of stress in early life may also potentiate adults' physiological vulnerability to stress in later life. The study tested this hypothesis by investigating whether the experience of stressful events and circumstances (SEC) in childhood or adolescence amplified the effect of adulthood SEC on physiological dysregulation (allostatic load, AL) in later midlife. Observational data were used in the present study. Physiological functioning was measured in later midlife (participants' age ranged from 49 to 63 years). Both childhood/adolescence and adulthood SEC were reported retrospectively on the same occasion. Participants were 5309 Danish men and women from Copenhagen Aging and Midlife Biobank (CAMB). SEC included socioeconomic and family factors. The AL index was based on nine cardiovascular, metabolic, and immune biomarkers.

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Analytic versus systemic group therapy for women with a history of child sexual abuse: one-year follow-up of a randomized controlled trial.Elkjaer H, Kristensen E, Mortensen EL, Poulsen S, Lau M. Psychology and Psychotherapy: Theory, Research and Practice. 87: 191-208, 2014.

Abstract:

This randomized prospective study examines durability of improvement in general symptomatology, psychosocial functioning and interpersonal problems, and compares the long-term efficacy of analytic and systemic group psychotherapy in women 1 year after completion of treatment for childhood sexual abuse. Women (n = 106) randomly assigned to analytic or systemic psychotherapy completed the Symptom Checklist-90-R, Global Assessment of Functioning, Global Life Quality, Registration Chart Questionnaire, and Flashback Registration at pre-treatment, post-treatment, and at a 1-year follow-up.

The impact of virtual admission on self-efficacy in patients with chronic obstructive pulmonary disease (COPD) – a randomized clinical trial. Emme C, Mortensen EL, Rydahl-Hansen S, Østergaard B, Schou L, Jakobsen AS, Phanareth K. Journal of Clinical Nursing. 21-22: 3124-3137, 2014.

Abstract:

To investigate how virtual admission during acute exacerbation influences self-efficacyin patients with chronic obstructive pulmonary disease, compared with conventional hospital admission. Telemedicine solutions have been highlighted as a possible way to increase self-efficacy inpatients with chronic diseases, such as chronic obstructive pulmonary disease. However, little is known about how telemedicine-based virtual admission as a replacement of hospital admission during acute exacerbation affectschronic obstructive pulmonary disease patients' self-efficacy. This study was a nonblinded, randomised clinical multicentre trial. The study was a substudy to TheVirtual Hospital, investigating the feasibility and safety of telemedicine-based treatment at home for patients with acute exacerbation of chronic obstructive pulmonary disease. Participants were consecutively randomised to virtual admission or conventional hospital admission. Data from 50 patients were analysed. Self-efficacy was assessed at baseline, three days after discharge, and also six weeks and three months after discharge, using the Danish version of 'The chronic obstructive pulmonary disease self-efficacy scale'.

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A register based study of long-term health care use before and after psychotherapy. Fenger M, Mortensen EL, Poulsen S, Lau M. Nordic Journal of Psychiatry. 68: 450-459, 2014.

Abstract:

Psychotherapeutic treatment for non-psychotic disorders is associated with significant reduction in patients' symptoms, and therefore it is believed that treatment improves health and decreases the need for additional healthcare. However, little is known about long-term changes in utilization of healthcare services. To investigate long-term changes in utilization of public healthcare services for patients referred to psychotherapeutic treatment. A pre-post study with 761 consecutive patients and 15,220 matched individuals in a matched population reference group. Data from a comprehensive set of healthcare services were collected from central registries for 4 years prior to intake and for 4 years after completion of treatment.

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Assessing fatigue in late-midlife: increased scrutiny of the multiple fatigue inventory-20 for community-dwelling subjects. Fieo RA, Mortensen EL, Lund R, Avlund K. Assessment. 21:706-12, 2014.

Abstract:

Previous methods examining the Multiple Fatigue Inventory-20 (MFI-20) fatigue questionnaire have been limited to classical test theory, for example, factor analytic approaches. We employed modern test theory to further strengthen the construct validity of the MFI-20 fatigue in a sample of healthy late-midlife subjects. Five subdimensions of perceived fatigue were examined in n = 7,233 subjects: general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue. Fatigue burden was compared across age groups (aged 48-52 vs. 57-63) and gender. Mokken item response theory was used to investigate dimensionality, monotonicity, and invariant item ordering (IIO). In both age groups, as well as by gender, the Motivation domain presented with weak scalability, suggesting that caution be exercised when interpreting sum scores. For all groupings, the strongest scaling properties were observed in the General Fatigue domain. However, the General Fatigue domain did not meet the property of IIO. Two domains (for all groupings) did meet the minimum criteria for the property of IIO: Physical Fatigue and Activity. Introducing model parameters for items served to enhance the interpretive power of the MFI-20, allowing for the identification of the most optimal scales. Poorly performing items were more easily identified, and person ability was assessed more accurately.

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Infant SES as a predictor of personality – is the association mediated by intelligence? Flensborg-Madsen T, Mortensen EL. PLoS ONE. 9: e103846, 2014.

Abstract:

Although research into the continuity and change of personality traits during a lifespan has been fairly extensive, little research has been conducted on childhood predictors of adult personality. We aimed to investigate the association between infant socioeconomic status (SES), and Eysenckpersonality traits in adulthood. An additional aim was to investigate whether intelligence and education may mediate this association. SES of 9125 children in the Copenhagen Perinatal Cohort was recorded at a 1-year examination. A subsample of this cohort, comprising 1182 individuals, participated in a follow-up at 20-34 years and was administered the Eysenck Personality Questionnaire (EPQ) which includes measures of neuroticism, extraversion, psychoticism and the so-called lie-scale. Associations of SES with each of the four personality traits were analysed by bivariate and partial correlations, and the mediating effects of intelligence and years of education were analysed.

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An association of adult personality with prenatal and early postnatal growth: the EPQ-lie-scale. Flensborg-Madsen T, Revsbech R, Sørensen HJ, Mortensen EL. BMC Psychology. 2: 8, 2014. 

Abstract:

Recent studies have noted differences in social acquiescence and interpersonal relations among adults born preterm or with very low birth weight compared to full term adults. In addition, birth weight has been observed to be negatively correlated with lie-scale scores in two studies. We attempted to replicate and extend these studies by examining young adult lie-scale scores in a Danish birth cohort. Weight, length and head circumference of 9125 children from the Copenhagen Perinatal Cohort were measured at birth and at 1, 3 and 6 years. A subsample comprising 1182 individuals participated in a follow-up at 20-34 years and was administered the Eysenck Personality Questionnaire (EPQ) which includes a lie-scale(indicating social acquiescence or self-insight). Associations between lie-scale scores and weight, length and head circumference respectively were analysed by multiple linear regression adjusting for single-mother status, parity, mother's age, father's age, parental social status, age at EPQ measurement, intelligence, and adult size.

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Increased all-cause mortality with psychotropic medication in Parkinson's disease and controls: A national register-based study. Frandsen R, Baandrup L, Kjellberg J, Ibsen R, Jennum P. Parkinsonism Relat Disord. 20:1124-8, 2014.

Abstract:

Use of medication and polypharmacy is common as the population ages and its disease burden increases. We evaluated the association of antidepressants, benzodiazepines, antipsychotics and combinations ofpsychotropic drugs with all-cause mortality in patients with Parkinson's disease (PD) and a matched group without PD. We identified 5861 PD patients and 31,395 control subjects matched by age, gender and marital status, and obtained register data on medication use and vital status between 1997 and 2007.

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Morbidity in early Parkinson's disease and prior to diagnosisFrandsen R, Kjellberg J, Ibsen R, Jennum P. Brain Behav. 4:446-52, 2014.

Abstract:

Nonmotor symptoms are probably present prior to, early on, and following, a diagnosis ofParkinson's disease. Nonmotor symptoms may hold important information about the progression of Parkinson's disease. To evaluated the total early and prediagnostic morbidities in the 3 years before a hospital contact leading to a diagnosis of Parkinson's disease. Retrospective morbidity data from Danish National Patient Registry records (1997-2007) of 10,490 adult patients with a secondary care diagnosis of Parkinson's disease were compared with 42,505 control cases.

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Hearts and minds: linking vascular rigidity and aerobic fitness with cognitive aging. Gauthier CJ, Lefort M, Mekary S, Desjardins-Crépeau L, Skimminge A, Iversen P, Madjar C, Desjardins M, Lesage F, Garde E, Frouin F, Bherer L, Hoge RD. Neurobiol Aging. 36: 304-314, 2014.

Abstract:

Human aging is accompanied by both vascular and cognitive changes. Although arteries throughout the body are known to become stiffer with age, this vessel hardening is believed to start at the level of the aorta and progress to other organs, including the brain. Progression of this vascular impairment may contribute to cognitive changes that arise with a similar time course during aging. Conversely, it has been proposed that regular exercise plays a protective role, attenuating the impact of age on vascular and metabolic physiology. Here, the impact of vasculardegradation in the absence of disease was investigated within 2 groups of healthy younger and older adults. Age-related changes in executive function, elasticity of the aortic arch, cardiorespiratory fitness, and cerebrovascular reactivity were quantified, as well as the association between these parameters within the older group. In the cohort studied, older adults exhibited a decline in executive functions, measured as a slower performance in a modified Stroop task (1247.90 ± 204.50 vs. 898.20 ± 211.10 ms on the inhibition and/or switching component, respectively) than younger adults. Older participants also showed higher aortic pulse wave velocity (8.98 ± 3.56 vs. 3.95 ± 0.82 m/s, respectively) and lower VO₂ max (29.04 ± 6.92 vs. 42.32 ± 7.31 mL O2/kg/min, respectively) than younger adults. 

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In Utero exposure to selective serotonin reuptake inhibitors and risk for autism spectrum disorder Gidaya NB, Lee BK, Burstyn I, Yudell M, Mortensen EL, Newschaffer CJ Journal of Autism and Developmental Disorders. 44: 2558- 2567, 2014.

Abstract:

We investigated whether there is an association between increased risk for autism spectrum disorders (ASD) andselective serotonin reuptake inhibitors (SSRIs) used during pregnancy. This study used Denmark's health and population registers to obtain information regarding prescription drugs, ASD diagnosis, and health and socioeconomic status. There were 1.5 % of cases and 0.7 % of controls exposed to SSRIs during the pregnancy period, and higher effect estimates observed with longer use. We found evidence that in utero exposure to SSRIs increases a child's risk associated with ASD. These results, while adding to the limited knowledge on prenatal pharmacological exposures as potential ASD risk factors, need to be balanced against the benefits of indicated medication use by pregnant mothers.

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Occupational characteristics and cognitive aging in the Glostrup 1914 Cohort.Gow AJ, Avlund K, Mortensen EL. Journal of Gerontology: Psychological Science. 69: 228-236, 2014.

Abstract:

The effect of occupational characteristics on cognitive change over 20 years was examined. Occupational characteristics--intellectual challenge, physical hazards, and psychological demands--were assessed in the Glostrup 1914 Cohort when aged 60 years, and cognitive ability was assessed by 4 cognitiveability tests at ages 60, 70, and 80.

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Leisure activity associated with cognitive ability level, but not cognitive change. Gow AJ, Avlund K, Mortensen EL. Frontiers in psychology. 5: article 1176, doi:10.3389/fpsych.2014.01176, 2014.

Abstract:

Although activity participation is promoted as cognitively protective, critical questions of causality remain. In a cohort followed every 5 years from age 75 to 85 years, potential reciprocal associations between level and change in leisure activity participation and level and change in cognitive abilities were examined. Participants in the Glostrup 1914 Cohort, a longitudinal study of aging, completed standardized cognitive ability tests and reported their leisure activity participation (11 activities defined a leisure activity score) at ages 75, 80, and 85. Higherleisure activity was associated with higher cognitive ability (significant correlations ranged from 0.15 to 0.31, p < 0.05). Between ages 75 and 85, participation in leisure activities and cognitive ability declined significantly. 

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Capillary pericytes regulate cerebral blood flow in health and disease. Hall CN, Reynell C, Gesslein B, Hamilton NB, Mishra A, Sutherland BA, O'Farrell FM, Buchan AM, Lauritzen M, Attwell D. Nature. 508(7494):55-60, 2014.

Abstract:

Increases in brain blood flow, evoked by neuronal activity, power neural computation and form the basis of BOLD (blood-oxygen-level-dependent) functional imaging. Whether blood flow is controlled solely by arteriole smooth muscle, or also by capillary pericytes, is controversial. We demonstrate that neuronal activity and the neurotransmitter glutamate evoke the release of messengers that dilate capillaries by actively relaxing pericytes. Dilation is mediated by prostaglandin E2, but requires nitric oxide release to suppress vasoconstricting 20-HETE synthesis. In vivo, when sensory input increases blood flow, capillaries dilate before arterioles and are estimated to produce 84% of the blood flow increase. In pathology, ischaemia evokes capillary constriction by pericytes. We show that this is followed by pericyte death in rigor, which may irreversibly constrict capillaries and damage theblood-brain barrier. Thus, pericytes are major regulators of cerebral blood flow and initiators of functional imaging signals. Prevention of pericyte constriction and death may reduce the long-lasting blood flow decrease that damages neurons after stroke.

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Psychosocial factors at work and the development of mobility limitations among adults in Denmark. Hansen ÅM, Darsø L, Manty M, Nilsson CJ, Christensen U, Lund R, Holtermann A, Avlund K. Scan J Pub Health. 42: 417-424, 2014. 

Abstract:

Psychosocial factors in the working environment have been shown to be associated with mobility limitations, but this has not yet been confirmed in a Danish population. We aimed to examine how psychosocial factors at workare related to developing mobility limitations in Denmark. This study is based on data from 2952 middle-aged men and women without mobility limitations in 2000.

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Social class differences in midlife physical performance. Hansen ÅM, Andersen LL, Skotte J, Christensen U, Mortensen OS, Molbo D, Lund R, Nilsson CJ, Avlund K. Journal of Aging and Health. 26: 88-105, 2014.

Garde AH, Molbo D, Avlund K. Social Gradient in Allostatic load among Danish men and women in late midlife. Hansen ÅM, Lund R, Bruunsgaard H, Rod NH, Garde AH, Molbo D, Avlund K. Journal of Aging and Health. 26: 72-87, 2014.

Abstract:

The objective of the present study is to describe the prevalence of allostatic load (AL) among Danishmen and women in late midlife, and if there is a social gradient in AL. A total of 5,420 participants from the Copenhagen Aging and Midlife Biobank (CAMB) aged 48 to 63 years (68.5% men, 31.5% women) underwent a health examination including standardized measures of height, weight, body fat, and blood pressure in 2009-2011. AL (range 0-14) was established by summing the scores of the poorest quartile for each of 14 biological variables related to the metabolic and immune systems. We found a social gradient in AL in late midlife among men and women living in Denmark. AL may be a potential biomarker for early aging in countries with a strong social welfare system. It is important for intervention studies to be aware of this type of biological vulnerability already present in late midlife.

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Subclinical Cognitive Decline in Middle-Age is Associated with Reduced Task-induced Deactivation of the Brain’s Default Mode Network. Hansen NL, Lauritzen M, Mortensen EL, Osler M, Avlund K, Fagerlund B, Rostrup E. Human Brain Mapping. 35: 4488-4498, 2014.

Abstract:

Cognitive abilities decline with age, but with considerable individual variation. The neurobiological correlate of this variation is not well described. Functional brain imaging studies have demonstrated reduced task-induceddeactivation (TID) of the brain's default mode network (DMN) in a wide range of neurodegenerative diseases involving cognitive symptoms, in conditions with increased risk of Alzheimer's disease, and even in advanced but healthy aging. Here, we investigated brain activation and deactivation during a visual-motor task in 185 clinically healthy males from a Danish birth cohort, whose cognitive function was assessed in youth and midlife. Using each individual as his own control, we defined a group with a large degree of cognitive decline, and a control group. When correcting for effects of total cerebral blood flow and hemoglobin level, we found reduced TID in the posterior region of the DMN in the cognitive decline group compared to the control group. Furthermore, increased visual activation response was found in the cognitive decline group, indicating that the TID reduction was not exclusively due to overall impaired vascular reactivity. These results suggest a neurobiological basis for subclinical cognitive declinein late midlife, which includes TID alterations similar to the pattern seen in patients with AD and mild cognitiveimpairment. Hence, TID reduction might be suggested as an early marker for subtle cognitive decline in aging.

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Resting brain perfusion and selected vascular risk factors in healthy elderly subjects. Henriksen OM, Jensen LT, Krabbe K, Guldberg P, Teerlink T, Rostrup E. PLoS ONE. 9(5):e97363, 2014.

Abstract:

Both cerebral hypoperfusion and vascular risk factors have been implicated in early aging of the brain and the development of neurodegenerative disease. However, the current knowledge of the importance of cardiovascular health on resting brain perfusion is limited. The aim of the present study was to elucidate the relation between brain perfusion variability and risk factors of endothelial dysfunction and atherosclerosis in healthy aged subjects. Thirty-eight healthy subjects aged 50-75 years old were included. Mean global brain perfusion was measured using magnetic resonance phase contrast mapping and regional brain perfusion by use of arterial spin labeling.

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Heterogeneity of treatment changes after psychodynamic therapy within a one year follow-up: A replication study. Jensen HJ, Mortensen EL, Lotz M. Scandinavian Journal of Psychology. 55: 168-179, 2014. 

Abstract:

Naturalistic psychotherapy effect studies commonly report effect sizes for the total sample. However, a previousstudy of SCL-90 Global Severity Index (GSI) improvement in a large outpatient sample used a cluster analytic strategy and reported clinical relevant outcome trajectories that could be grouped into early within-treatmentimprovement, late improvement in the follow-up period, and deteriorating patients with slight improvement that was lost at follow-up. We explore GSI outcome trajectories and clinical significant change in a sample of 320 patients at a public psychiatric outpatient psychodynamic group therapy unit, the majority with anxiety, personality, and mood disorders. The study revealed large discharge and follow-up effect sizes but more than one third of the patients were without measurable improvement. The major clusters described above were confirmed, and revealed unique clinical and socio-demographic characteristics. Late improvers, as compared with early improvers, were characterized by anxiety symptoms and lack of network support after controlling for GSI at admission. Similarly, deteriorating patients had longer duration of illness and less favourable social characteristics compared with the other two groups. 

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Health, social and economic consequences of hypersomnia: a controlled national study from a national registry evaluating the societal effect on patients and their partners. Jennum P, Ibsen R, Avlund K, Kjellberg J. Eur J Health Econ. 15:303-11, 2014.

Abstract:

Hypersomnia causes significant socioeconomic burden, but there is insufficient information about the time course and the effect on the partner. The aim of this study was to estimate the factual direct and productivity costs ofhypersomnia in a controlled study including all national patients and their partners. Using records from the DanishNational Patient Registry (1997-2009), we identified all patients with a diagnosis of hypersomnia and compared these patients and their partners with randomly chosen controls matched for age, gender, geographic area and marital status. Direct and productivity costs, including frequencies of primary and sector contacts and procedures, medication, labour supply and social transfer payments were extracted from the national databases. A total of 2,855 national patients was compared to 11,382 controls. About 70 % of patients and controls were married or cohabiting. Patients with hypersomnia had significantly higher rates of health-related contact, medication use and socioeconomic cost. 

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Health, Social and Economic Consequences of Polyneuropathy: A Controlled National Study Evaluating Societal Effects on Patients and Their Partners. Jennum P, Ibsen R, Kjellberg J. Eur Neurol. 73:81-88, 2014.

Abstract:
To estimate the direct and indirect factual costs of polyneuropathy in a national sample of patientsand their spouses based on a national register-based cohort study with matched controls. Using records from the Danish National Patient Registry (1997-2009) all patients with a diagnosis ofpolyneuropathy and their partners were identified and compared with randomly chosen controls matched for age, gender, geographic area and civil status. Direct costs included frequencies of primary and secondary sector contacts and procedures, and medication. Indirect costs included the effect on labor supply. Social-transfer payments were included to illustrate the effect on national accounts. All cost data were extracted from nationaldatabases.

Cardiovascular and lung function in relation to outdoor and indoor exposure to fine and ultrafine particulate matter in middle-aged subjects. Karottki DG, Bekö G, Clausen G, Madsen AM, Andersen ZJ, Massling A, Ketzel M, Ellermann T, Lund R, Sigsgaard T, Møller P, Loft S. Environment International. 73: 372-81, 2014.

Abstract:

This cross-sectional study investigated the relationship between exposure to airborne indoor and outdoor particulatematter (PM) and cardiovascular and respiratory health in a population-based sample of 58 residences in Copenhagen, Denmark. Over a 2-day period indoor particle number concentrations (PNC, 10-300 nm) and PM2.5 (aerodynamic diameter<2.5 μm) were monitored for each of the residences in the living room, and outdoor PNC (10-280 nm), PM2.5 and PM10 (aerodynamic diameter<10 μm) were monitored at an urban background station in Copenhagen. In the morning, after the 2-day monitoring period, we measured microvascular function (MVF) andlung function and collected blood samples for biomarkers related to inflammation, in 78 middle-aged residents. Bacteria, endotoxin and fungi were analyzed in material from electrostatic dust fall collectors placed in the residences for 4 weeks. Data were analyzed using linear regression with the generalized estimating equation approach. Statistically significant associations were found between indoor PNC, dominated by indoor use of candles, and lower lung function, the prediabetic marker HbA1c and systemic inflammatory markers observed as changes in leukocyte differential count and expression of adhesion markers on monocytes, whereas C-reactive protein was significantly associated with indoor PM2.5. The presence of indoor endotoxin was associated with lower lung function and expression of adhesion markers on monocytes. An inverse association between outdoorPNC and MVF was also statistically significant. The study suggests that PNC in the outdoor environment may be associated with decreased MVF, while PNC, mainly driven by candle burning, and bioaerosols in the indoorenvironment may have a negative effect on lung function and markers of systemic inflammation and diabetes.

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The association of pre-pregnancy alcohol drinking with child neuropsychological functioning. Kesmodel US, Kjaersgaard MIS, Denny CH, Bertrand J, Skogerbø Å, Eriksen HF, Bay B, Underbjerg M, Mortensen EL. BJOG. Accepted, 2014.

Abstract: 
To examine the effects of prepregnancy alcohol drinking on child neuropsychological functioning. Prospective follow-up study. 154 women and their children sampled from the Danish National Birth Cohort. Participants were sampled based on maternal alcohol consumption before pregnancy. At 5 years of age, the children were tested with the Wechsler Preschool and Primary Scale of Intelligence-Revised, the Test of Everyday Attention for Children at Five (TEACh-5), and the Movement Assessment Battery for Children (MABC). The Behaviour Rating Inventory of Executive Function (BRIEF) was completed by the mothers and a preschool teacher. Parental education, maternal IQ, prenatal maternal smoking, child's age at testing, child's sex, and maternal alcohol intake during pregnancy were considered potential confounders.

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Hypnotics and mortality – confounding by disease and socioeconomic position? Kriegbaum M, Hendriksen C, Vass M, Mortensen EL, Osler M. Pharmacoepidemiology and Drug Safety. Accepted, 2014.

Abstract:
The aim of this Cohort study of 10 527 Danish men was to investigate the extent to which the association between hypnotics and mortality is confounded by several markers of disease and living conditions. Exposure was purchases of hypnotics 1995-1999 ("low users" (150 or less defined daily dose (DDD)) or "high users" (151 or more DDD)). Follow-up for all-cause mortality was from 1 Jan 2000 to 19 June 2010. Cox proportional hazard models were used to study the association. Covariates were entered one at a time and simultaneously. Results were reported using hazard ratio (HR) and 95% confidence intervals (CI).

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Childhood socioeconomic position, young adult intelligence and fillings of prescribed medicine for prevention of cardiovascular disease in middle-aged men. Kriegbaum M, Kildemoes HW, Rasmussen JN, Hendriksen C, Vass M, Mortensen EL, Osler M. BMJ Open. 4(1): e004178, 2014.

Abstract:

To explore the relationship between childhood socioeconomic position (SEP) and filling of medicine prescriptions for prevention of cardiovascular diseases (CVDs), with young adultintelligence (IQ) as a potential mediator. Birth cohort study with logistic and Cox-proportional hazard regression analyses of associations between childhood SEP, retrieved from birth certificates, and prevalence, initiation of and refill persistency for CVD preventive medicine. Denmark. 8736 Danish men born in 1953, who had no CVD at the start of follow-up in 1995, were followed in the Danish National Prescription Register for initiation of and refill persistency for antihypertensives and statins, until the end of 2007 (age 54 years).


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Hypnotics and mortality – partial confounding by disease, substance abuse and socioeconomic factors? Kriegbaum M, Kildemoes HW, Rasmussen JN, Hendriksen C, Vass M, Mortensen EL, Osler. Pharmacoepidemiology & Drug Safety. Accepted, 2014.

Abstract:

The aim of this Cohort study of 10 527 Danish men was to investigate the extent to which the association between hypnotics and mortality is confounded by several markers ofdisease and living conditions. Exposure was purchases of hypnotics 1995-1999 ("low users" (150 or less defined daily dose (DDD)) or "high users" (151 or more DDD)). Follow-up for all-cause mortality was from 1 Jan 2000 to 19 June 2010. Cox proportional hazard models were used to study the association. Covariates were entered one at a time and simultaneously. Results were reported using hazard ratio (HR) and 95% confidence intervals (CI).

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Stressful social relations and mortality. A prospective cohort study. Lund R, Christensen U, Kriegbaum M, Nilsson CJ, Rod N. Journal of Epidemiology and Community Health. 68:720-7, 2014.

Abstract:

Few studies have examined the relationship between stressful social relations in private life and all-cause mortality. To evaluate the association between stressful social relations (with partner, children, other family, friends and neighbours, respectively) and all-cause mortality in a large population-based study of middle-aged men and women. Further, to investigate the possible modification of this association by labour force participation and gender. We used baseline data (2000) from The Danish Longitudinal Study on Work, Unemployment and Health, including 9875 men and women aged 36-52 years, linked to the Danish Cause of Death Registry for information on all-cause mortality until 31 December 2011. Associations between stressful social relations with partner, children, other family, friends and neighbours, respectively, and all-cause mortality were examined using Cox proportional hazards models adjusted for age, gender, cohabitation status, occupational social class, hospitalisation with chronic disorder 1980-baseline, depressive symptoms and perceived emotional support. Modification by gender and labour force participation was investigated by an additive hazards model.

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Face and content validation of a measure of social relations.Lund R, Nielsen LS, Schmidt L, Henriksen PE, Avlund K, Christensen U. Journal of Aging and Health 2014. 26:128-50, 2014.

Abstract:

The aim of the present article is to describe the face and content validity as well as reliability of the Copenhagen Social Relations Questionnaire (CSRQ). The face and content validity test was based on focus group discussions and individual interviews with 31 informants. Another 94 men and women participated in an 8-day test-retest analysis.

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Negative aspects of close social relations and 10 year incident ischemic heart disease hospitalization among middle-aged Danes. Lund R, Rod NH, Nilsson CJ, Thielen K, Christensen U. Eur J Prev Card. 21:1249-1256, 2014.

Abstract:

Little is known about the association between negative aspects of close socialrelations and development of ischaemic heart disease (IHD). We aim to address if the experience of worries/demands and conflicts with close social relations are related to risk of first-timehospitalization with IHD and whether emotional support can buffer this effect. A total of 8550 randomly selected men and women aged 36-52 years free of earlier IHD hospitalization at baseline in 2000 were followed prospectively for first-time hospitalization with IHD (ICD10: I21-25) through 2010 in the Danish National Patient Registry. Cox regression analysis was used to analyse data and all analyses were adjusted for age, gender, social class, cohabitation, and depressive symptoms.

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Association of Physical Workload and Leisure Time Physical Activity with Incident Mobility Limitation: A Follow-up Study. Mänty M, Møller A, Nilsson C, Lund R, Christensen U, Avlund K. Occupational and Environmental Medicine. 71:543-8, 2014.

Abstract:

To examine individual as well as joint associations of physical workload and leisure time physical activity with incident mobility limitations in initially well-functioning middle-aged workers. This study is based on 6-year follow-up data of the Danish Longitudinal Study on Work, Unemployment and Health. Physical workload was reported at baseline and categorised as light, moderate or heavy. Baseline leisure time physical activity level was categorised as sedentary or active following the current recommendations on physical activity. Incidence of mobilitylimitations in climbing stairs and running among initially well-functioning workers (n=3202 and n=2821, respectively) was assessed during follow-up.

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Intelligence in early adulthood and mortality from natural and unnatural causes in middle-aged Danish men. Meincke RH, Mortensen EL, Avlund K, Rosthøj S, Sørensen H J, Olser M. Journal of Epidemiology and Community Health. 68: 130-136, 2014.

Abstract:

High intelligence early in life has consistently been associated with decreasedmortality, but the mechanisms are still not fully understood. In this cohort study, we examined the association between intelligence in early adulthood and later mortality from natural and unnaturalcauses taking birth weight, parental socioeconomic position, participants' own education and body mass index into account. 13 536 Danish men born in 1953 and 1959-1961 with data from birth certificates andintelligence test scores from conscription were followed until 2009. Information on vital status was obtained from the Civil Registration System. Mortality risks were analysed by the multiple Cox proportional hazards model.

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A longitudinal cohort study of intelligence and later hospitalisation with mental disorder. Mikkelsen SS, Flensborg-Madsen T, Eliasen M, Mortensen EL. Comprehensive Psychiatry. 55: 912-919, 2014.

Abstract:

Few studies on the associations between pre-morbid IQ and mental disorders are based on comprehensive assessment of intelligence in both women and men and include a wide range of confounding variables. Thus, the objective of the present study was to examine the association between pre-morbid IQ and hospitalisation with any mental disorder, including possible gender differences in the association. The study population was born in 1959-61 and premorbid IQ was assessed with the WAIS between 1982 and 1994. Information on mental disorders was obtained from Danish hospital registers with a mean follow-up interval of 21.1years. A total of 1106 participants were analysed.

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A prospective cohort study of quality of life and ischemic heart disease. Mikkelsen SS, Mortensen EL, Flensborg-Madsen T. Scandinavian Journal of Public Health. 42: 60-66, 2014.

Abstract:

To examine the role of self-rated quality of life, as a whole, on the risk of developingischemic heart disease. Information on self-rated quality of life and covariates was obtained from 4497 people from the Copenhagen Perinatal Cohort. The study population, consisting of both men and women aged 31-33 years at baseline, was followed for registration of ischemic heart disease in national registers. Two different follow-up periods were examined.

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Smoking and drinking as risk indicators for tooth loss in middle-aged Danes. Morse DE, Avlund K, Christensen LB, Fiehn NE, Molbo D, Holmstrup P, Kongstad J, Mortensen EL, HolmPedersen P. Journal of Aging and Health. 26: 54-71, 2014.

Abstract:

To investigate tobacco and alcohol consumption as risk indicators for missing teeth in late middle-aged Danes. In all, 1,517 Copenhagen Aging and Midlife Biobank (CAMB) participants received a clinical oral examination that included number of teeth. Information on smoking, drinking, and various covariates was obtained using self-administered, structured questionnaires. Descriptive statistics and logistic regression (dependent variable: 6+ vs. <6 missing teeth) were used to investigate smoking and drinking in relation to missing teeth.

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The relationship between cognitive ability and demographic factors in late midlife. Mortensen EL, Flensborg-Madsen T, Molbo D, Fagerlund B, Christensen U, Lund R, Osler M, Avlund K. Journal of Aging and Health. 26: 37-53, 2014.

Abstract:

The aim of the article is to analyze associations between sex, age, education, and social class and cognitive ability in late midlife and to evaluate differences in cognitive abilityamong the three Copenhagen Aging and Midlife Biobank (CAMB) cohorts. The sample comprised 5,417 CAMB participants from three cohorts with scores on the Intelligenz-Struktur-Test 2000 R (I-S-T 2000 R).

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Personality in late midlife. Associations with with demographic factors and cognitive ability. Mortensen EL, Flensborg-Madsen T, Molbo D, Christensen U, Osler M, Avlund K, Lund R. Journal of Aging and Health. 26: 21-36, 2014.

Abstract:

To analyze associations in late midlife between sex, age, education and social class, and the Big Five personality traits; to analyze associations between personality traits andcognitive ability in late midlife; and to evaluate how these associations are influenced bydemographic factors. The study sample comprised 5,397 late midlife participants from three cohorts who had completed the NEO Five-Factor Inventory (NEO-FFI) and a measure of cognitive ability.

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Mobility Decline in Old Age: The Combined Effect of Mobility-Related Fatigue and Socioeconomic Position. Nilsson CJ, Siersma V, Mänty M, Vass M, Avlund K, Lund R. Journal of Epidemiology and Community Health. 68: 510-5, 2014.

Abstract:

Mobility-related fatigue and low socioeconomic position predicts mobilitylimitations and disability in old age, but the interplay between these two factors is unknown. To evaluate whether mobility-related fatigue is a stronger risk factor for mobility limitations in certainsocioeconomic groups, the aim of this study was to examine the combined effect of mobility-related fatigue and socioeconomic position on mobility limitations in a prospective study among older Danish men and women. Multivariate linear regression models with combined exposure variables using generalised estimating equations were performed using four waves of data on 2874 individuals without mobility limitations at baseline from The Danish Intervention Study on Preventive Home Visits.

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Prevalence and Predictors of Personality Change after Severe Brain Injury. Norup A, Mortensen EL. Archives Phys Med Rehabil. Accepted, 2014.

Abstract:

To investigate the prevalence of personality change after severe brain injury; to identify predictors of personality change; and to investigate whether personality change is associated with distress in family members. A longitudinal study of personality change. Rehabilitation unit. The study sample was composed of 22 pairs of patients with traumatic braininjury or nontraumatic brain injury (N=22) and their significant others (SOs). Not applicable. An SO completed the observer version of the NEO Five Factor Inventory rating the patient at discharge from hospital and 1 year after injury. The SOs were also asked to complete the anxiety and depression scales of the Symptom Checklist-90-Revised, rating their own emotional condition and health-related quality of life (HRQOL) as assessed by the 4 mental scales of the Medical Outcomes Study 36-Item Short-Form Health Survey.

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Excluding the typical Patients in Thirty Years of Pharmacotherapy Efficacy Trials for Obsessive Compulsive Disorder. Odlaug B, Weinhandl E, Mancebo MC, Mortensen EL, Eisen KL, Rasmussen SA, Schreiber LRN, Grant JE. Annals of Clinical Psychiatry. 26: 39-46, 2014.

Abstract: 
Over the past 30 years, clinical trials have resulted in several successful pharmacotherapies for obsessive-compulsive disorder (OCD), yet patients in clinical settings often report inadequate response. This study compares clinical characteristics of treatment-seeking OCDpatients to the inclusion/exclusion criteria used in pharmacotherapy trials. The sample consisted of 325 community members with a DSM-IV diagnosis of OCD who underwent systematic interviews with clinicians knowledgeable in the diagnosis and treatment of OCD. We compiled pharmacotherapy studies for OCD published between 1980 and 2010 using Medline, PubMed, and library resources, and estimated the proportion of patients in each decade satisfying the most common inclusion/exclusion criteria.

Educational intervention and functional decline among older people: the modifying effects of social capital. Poulsen T, Siersma VD, Lund R, Christensen U, Avlund K. Scand J Public Health. 42:295-303, 2014.

Abstract:

To analyse if social capital modifies the effect of educational intervention of home visitors on mobility disability. Earlier studies have found that educational intervention of home visitors has a positive effect of older peoples' functional decline, but how social capital might modify this effect is still unknown. We used the Danish Intervention Study on Preventive Home Visits - a prospective cohort study including 2863 75-year-olds and 1171 80-year-olds in 34 Danish municipalities - to analyse the modifying effect of different aspects of social capital on the effect of educationalintervention of home visitors on functional decline. The three measures of social capital (bonding, bridging, and linking) were measured at contextual level. Data was analysed with multivariate linear regression model using generalised estimating equations to account for repeated measurements.

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 Health care service use before and after a natural disaster in survivors with and without PTSD: A prospective and retrospective cohort study. Rosendal S, Mortensen EL, Andersen H, Heir T. Psychiatric Services. 65: 91-97, 2014.

Childhood dyspraxia predicts adult-onset schizophrenia spectrum disorder. Schiffman J, Mittal V, Kline E, Michelsen N, Ekstrøm M, Mortensen EL, Mednick S, Sørensen HJ. Development and Psychopathology. Accepted, 2014.

Abstract:

Several neurological variables have been investigated as premorbid biomarkers of vulnerability for schizophrenia and other related disorders. The current study examined whether childhood dyspraxia predicted later adult nonaffective-psychosis-spectrum disorders. From a standardized neurological examination performed with children (aged 10-13) at genetic high risk of schizophrenia and controls, several measures of dyspraxia were used to create a scale composed of face/head dyspraxia, oral articulation, ideomotor dyspraxia (clumsiness), and dressing dyspraxia (n = 244). Multinomial logistic regression showed higher scores on the dyspraxia scale predict nonaffective-psychosis-spectrum disorders relative to other psychiatric disorders and no mental illness outcomes, even after controlling for genetic risk, χ2 (4, 244) = 18.61, p < .001. Findings that symptoms of dyspraxia in childhood (reflecting abnormalities spanning functionally distinct brain networks) specifically predict adult nonaffective-psychosis-spectrum disorders are consistent with a theory of abnormal connectivity, and they highlight a marked early-stage vulnerability in the pathophysiology of nonaffective-psychosis-spectrum disorders.

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Personality Characteristics in surgery seeking and non-surgery seeking obese individuals compared to non-obese controls. Stenbæk D, Hjordt LV, Haahr ME, Worm D, Hansen DL, Mortensen EL, Knudsen GM. Eating Behaviours. 15: 595.

Abstract:

It is currently unknown what makes some obese individuals opt for bariatric surgery whereas others choose not to. The aim of this study was to examine whether personality characteristics differed between obese individuals signed up for Roux-en-Y gastric bypass (RYGB) (N=30) and obeseindividuals not seeking RYGB (N=30) compared to non-obese controls (N=30). All participants completed the NEO Personality Inventory-Revised. The obese RYGB group displayed higher levels of Neuroticism and borderline lower levels of Extraversion compared to the obese non-RYGB and thenon-obese group, while the two latter groups did not differ in terms of personality. The Neuroticism domain and possibly the Extraversion domain may therefore be worthwhile to consider in future studies investigating the outcome of bariatric surgery.

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Does Harm Avoidance mediate effects of recollected parental bonding on mental distress in adulthood? Stenbæk DS, Jensen CG, Holst KK, Mortensen EL, Knudsen GM, Frokjaer VG. Comprehensive Psychiatry. 55: 1007-1014, 2014. 

Abstract:

Adverse early life conditions such as perceived low quality of parental bonding increase vulnerability to stress and psychopathology in adulthood. However, the mechanisms by which perceptions of parental bonding translate into vulnerability are unclear and remain sparsely investigated in healthy populations. We proposed a model, in which the personality trait Harm Avoidance would mediate effects of recollectedparental bonding during the first sixteen years of life on measures of perceived stress and mental distress severity in adulthood. Five-hundred-eighteen adults (65.1 % women), aged 18-53years, completed questionnaires of parental bonding, perceived stress, traitHarm Avoidance, and severity of mental distress. Direct and indirect effects mediated through trait Harm Avoidance were examined in a structural equation model.

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Associations between xerostomia, histopathological alterations, and autonomic innervation of labial salivary glands in men in late midlife. Sørensen CE, Larsen JO, Reibel J, Lauritzen M, Mortensen EL, Osler M, Pedersen AM. Experimental Gerontology. 57: 211-217, 2014.

Abstract:

One aim of the present study was to investigate whether symptoms of oral dryness (xerostomia) during daytime, assessed in a study group of middle-aged male positive and negative outliers in cognition scores, were associated with age-related degenerative changes in human labialsalivary glands and with quantitative measures of the glandular autonomic innervation. Another aim was to study the relation between the autonomicinnervation and loss of secretory acinar cells in these glands. Labial salivary gland biopsies were taken from the lower lip from 190 men, born in 1953 and members of the Danish Metropolit birth cohort, who were examined for age-related changes in cognitive function and dental health as part of the Copenhagen University Center for Healthy Aging clinical neuroscience project. The glands were routinely processed and semi-quantitatively analyzed for inflammation, acinar atrophy, fibrosis, and adipocyte infiltration. Sections of labial salivary gland tissue were stained with the panneuronal marker PGP 9.5. In a subsample of 51 participants, the autonomic innervation of the glands was analyzed quantitatively by use of stereology.

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Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: the CARTA consortium. Taylor AE, … Mortensen EL (among 62 members of the CATA consortium).

Abstract:

To investigate whether associations of smoking with depression and anxiety are likely to be causal, using a Mendelian randomisationapproach. Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730) as a proxy for smoking heaviness, and observational meta-analyses of the associations of smoking status and smoking heaviness with depression, anxiety and psychological distress. Current, former and never smokers of European ancestry aged ≥16 years from 25 studies in the Consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA). Binary definitions of depression, anxiety and psychological distress assessed by clinical interview, symptom scales or self-reported recall of clinician diagnosis.

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Psycological predictors of mental health and health-related quality of life after bariatric surgery: A review of the recent research. Wimmelmann CL, Dela F, Mortensen EL. Obs Res Clin Pract. 8: e314-e324, 2014.

Abstract:

Improvement of mental health and health-related quality of life (HRQOL) is an important success criterion for bariatric surgery. In general, mental health and HRQOL improve after surgery, but some patients experience negative psychological reactions postoperatively and the influence of pre-surgical psychological factors on mental wellbeing after surgery is unclear. The aim of the current article therefore is to review recentresearch investigating psychological predictors of mental health and HRQOL outcome. We searched PubMed, PsycInfo and Web of Science for studies investigating psychological predictors of either mental health or HRQOL after bariatric surgery. Original prospective studies published between 2003 and 2012 with a sample size >30 and a minimum of 1 year follow-up were included.

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Psycological predictors of weight loss after bariatric surgery: A review of the recent research. Wimmelmann CL, Dela F, Mortensen EL. Obs Res Clin Pract. 8: e299-e313, 2014. 

Abstract:

Improvement of mental health and health-related quality of life (HRQOL) is an important success criterion for bariatric surgery. In general, mental health and HRQOL improve after surgery, but some patients experience negative psychological reactions postoperatively and the influence of pre-surgical psychological factors on mental wellbeing after surgery is unclear. The aim of the current article therefore is to review recentresearch investigating psychological predictors of mental health and HRQOL outcome. We searched PubMed, PsycInfo and Web of Science for studies investigating psychological predictors of either mental health or HRQOL after bariatric surgery. Original prospective studies published between 2003 and 2012 with a sample size >30 and a minimum of 1 year follow-up were included.

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The psychological profile of bariatric patients with and without type 2 diabetes: Baseline results of the longitudinal GASMITO-PSYC study. Wimmelmann CL, Smith E, Lund MT, Hansen M, Dela F, Mortensen EL. Surgery for Obesity and Related Diseases. In press, 2014.

Abstract:
Some bariatric patients are referred for surgery with a diagnosis of type 2 diabetes while others are referred without co-morbiddiabetes, but psychological differences between patients with and without type 2 diabetes undergoing bariatric surgery have not yet been investigated. The objective of this study was to present the baseline results of the longitudinal GASMITO-PSYC study, and to evaluate thepsychological differences between bariatric patients with and without type 2 diabetes. A total of 129 Roux-en- Y gastric bypass patients were recruited from the bariatric clinic at a hospital in the suburban Copenhagen area. Participants answered questionnaires concerning personality, mental symptoms, health-related quality of life (HRQOL), body image, lifestyle, and physical health including diabetes status on average 11 weeks before surgery. Questionnaires were either sent to the participant's home address or administered at the University of Copenhagen.

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Overexpression of DNA ligase III in mitochondria protects cells against oxidative stress and improves mitochondrial DNA base excision repair. Akbari M, Keijzers G, Maynard S, Scheibye-Knudsen M, Desler C, Hickson ID, Bohr VA. DNA Repair. 16: 44–53, 2014.

Abstract:

Base excision repair (BER) is the most prominent DNA repair pathway in human mitochondria. BER also results in a temporary generation of AP-sites, single-strand breaks and nucleotide gaps. Thus, incomplete BER can result in the generation of DNA repair intermediates that can disruptmitochondrial DNA replication and transcription and generate mutations. We carried out BER analysis in highly purified mitochondrial extracts from human cell lines U2OS and HeLa, and mouse brain using a circular DNA substrate containing a lesion at a specific position. We found that DNAligation is significantly slower than the preceding mitochondrial BER steps. Overexpression of DNA ligase III in mitochondria improved the rate of overall BER, increased cell survival after menadione induced oxidative stress and reduced autophagy following the inhibition of the mitochondrialelectron transport chain complex I by rotenone. Our results suggest that the amount of DNA ligase III in mitochondria may be critical for cell survival following prolonged oxidative stress, and demonstrate a functional link between mitochondrial DNA damage and repair, cell survival upon oxidativestress, and removal of dysfunctional mitochondria by autophagy.

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Glucose-dependent insulinotropic polypeptide has impaired effect on abdominal, subcutaneous adipose tissue metabolism in obese subjects. Asmar M, Simonsen L, Arngrim N, Holst JJ, Dela F, Bülow J. Int J Obes (Lond). 38: 259- 265, 2014.

Abstract:

Glucose-dependent insulinotropic polypeptide (GIP) appears to have a role in lipid metabolism. Recently, we showed that GIP in combination with hyperinsulinemia and hyperglycemia increases triglyceride uptake in abdominal, subcutaneous adipose tissue in lean humans. It has been suggested that increased GIP secretion in obesity will promote lipid deposition in adipose tissue. In light of the current attempts to employ GIP antagonists in the treatment and prevention of human obesity, the present experiments were performed in order to elucidate whether the adiposetissue lipid metabolism would be enhanced or blunted during a GIP, hyperinsulinemic and hyperglycemic (HI-HG) clamp in obese subjects with either normal glucose tolerance (NGT) or impaired glucose tolerance (IGT). Sixteen obese (BMI>30 kg m(-2)) subjects were divided into two groups, based on their plasma glucose response to an oral glucose challenge: (i) NGT and (ii) IGT. Abdominal, subcutaneous adipose tissue lipid metabolism was studied by conducting measurements of arteriovenous concentrations of metabolites and regional adipose tissue blood flow (ATBF) during GIP (1.5 pmol kg(-1) min(-1)) in combination with a HI-HG clamp.

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The dual nature of mismatch repair as antimutator and mutator: for better or for worse. Bak ST, Sakellariou D, Pena-Diaz J. Frontier in Genetics. 5: 287, 2014.

Abstract:

DNA is constantly under attack by a number of both exogenous and endogenous agents that challenge its integrity. Among the mechanisms that have evolved to counteract this deleterious action, mismatch repair (MMR) has specialized in removing DNA biosynthetic errors that occur when replicating the genome. Malfunction or inactivation of this system results in an increase in spontaneous mutability and a strong predisposition to tumor development. Besides this key corrective role, MMR proteins are involved in other pathways of DNA metabolism such as mitotic and meiotic recombination and processing of oxidative damage. Surprisingly, MMR is also required for certain mutagenic processes. The mutagenic MMR has beneficial consequences contributing to the generation of a vast repertoire of antibodies through class switch recombination and somatic hypermutation processes. However, this non-canonical mutagenic MMR also has detrimental effects; it promotes repeat expansions associated with neuromuscular and neurodegenerative diseases and may contribute to cancer/disease-related aberrant mutations and translocations. The reaction responsible for replication error correction has been the most thoroughly studied and it is the subject to numerous reviews. This review describes briefly the biochemistry of MMR and focuses primarily on the non-canonical MMR activities described in mammals as well as emerging research implicating interplay of MMR and chromatin.

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Bengt Saltin (1935-2014) Memorial. Bangsbo J, Kjaer M, Hellsten Y. J Physiol. 592: 5149-5151, 2014. 

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Release of tensile strain on engineered human tendon tissue disturbs cell adhesions, changes matrix architecture, and induces an inflammatory phenotype. Bayer ML, Schjerling P, Herchenhan A, Zeltz C, Heinemeier KM, Christensen L, Krogsgaard M, Gullberg D, Kjaer M. PLoS One. 9:e86078, 2014.

Abstract:

Mechanical loading of tendon cells results in an upregulation of mechanotransduction signaling pathways, cell-matrix adhesion and collagen synthesis, but whether unloading removes these responses is unclear. We investigated the response to tension release, with regard to matrixproteins, pro-inflammatory mediators and tendon phenotypic specific molecules, in an in vitro model where tendon-like tissue was engineered fromhuman tendon cells. Tissue sampling was performed 1, 2, 4 and 6 days after surgical de-tensioning of the tendon construct. When tensile stimulus was removed, integrin type collagen receptors showed a contrasting response with a clear drop in integrin subunit α11 mRNA and protein expression, and an increase in α2 integrin mRNA and protein levels. Further, specific markers for tendon cell differentiation declined and normal tendonarchitecture was disturbed, whereas pro-inflammatory molecules were upregulated. Stimulation with the cytokine TGF-β1 had distinct effects on some tendon-related genes in both tensioned and de-tensioned tissue. These findings indicate an important role of mechanical loading for cellular and matrix responses in tendon, including that loss of tension leads to a decrease in phenotypical markers for tendon, while expression of pro-inflammatory mediators is induced.

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Distinct dynamics for DNA repair proteins in the nucleoplasm, nucleoli and at sites of DNAdamage. Bendtsen KM, Jensen MB, May A, Rasmussen LJ,Bohr VA, Jensen MH,Trusina A. Eur Biophys J. 43:509–516, 2014.

Abstract:

We have investigated the mobility of two EGFP-tagged DNA repair proteins, WRN and BLM. In particular, we focused on the dynamics in two locations, the nucleoli and the nucleoplasm. We found that both WRN and BLM use a "DNA-scanning" mechanism, with rapid binding-unbinding to DNA resulting in effective diffusion. In the nucleoplasm WRN and BLM have effective diffusion coefficients of 1.62 and 1.34 μm(2)/s, respectively. Likewise, the dynamics in the nucleoli are also best described by effective diffusion, but with diffusion coefficients a factor of ten lower than in the nucleoplasm. From this large reduction in diffusion coefficient we were able to classify WRN and BLM as DNA damage scanners. In addition to WRN and BLM we also classified other DNA damage proteins and found they all fall into one of two categories. Either they are scanners, similar to WRN and BLM, with very low diffusion coefficients, suggesting a scanning mechanism, or they are almost freely diffusing, suggesting that they interact with DNA only after initiation of a DNA damage response.

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Effects of hydrolysed casein, intact casein and intact whey protein on energy expenditure and appetite regulation: a randomized, controlled, cross-over study. Bendtsen LQ, Lorenzen JK, Gomes S, Liaset B, Holst JJ, Ritz C, Reitelseder S, Sjödin A, Astrup A. British Journal of Nutrition. 112: 1412-22, 2014. 

Abstract:

Casein and whey differ in amino acid composition and in the rate of absorption; however, the absorption rate of casein can be increased to mimic that of whey by exogenous hydrolysis. The objective of the present study was to compare the effects of hydrolysed casein (HC), intact casein (IC) and intact whey (IW) on energy expenditure (EE) and appetite regulation, and thereby to investigate the influence of amino acid composition and the rate of absorption. In the present randomised cross-over study, twenty-four overweight and moderately obese young men and women consumed three isoenergetic dietary treatments that varied in protein source. The study was conducted in a respiration chamber, where EE, substrate oxidation and subjective appetite were measured over 24 h at three independent visits. Moreover, blood and urine samples were collected from the participants. The results showed no differences in 24 h and postprandial EE or appetite regulation. However, lipid oxidation, estimated from the respiratory quotient (RQ), was found to be higher after consumption of IW than after consumption of HC during daytime (P= 0·014) as well as during the time after the breakfast meal (P= 0·008) when the food was provided. Likewise, NEFA concentrations were found to be higher after consumption of IW than after consumption of HC and IC (P< 0·01). However, there was no overall difference in the concentration of insulin or glucagon-like peptide 1. In conclusion, dietary treatments when served as high-protein mixed meals induced similar effects on EE and appetite regulation, except for lipid oxidation, where RQ values suggest that it is higher after consumption of IW than after consumption of HC.

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Lactate transport and signaling in the brain: potential therapeutic targets and roles in body-brain interaction. Bergersen LH. J Cereb Blood Flow Metab. [Epub ahead of print], 2014.

Abstract:

Lactate acts as a 'buffer' between glycolysis and oxidative metabolism. In addition to being exchanged as a fuel by the monocarboxylate transporters (MCTs) between cells and tissues with different glycolytic and oxidative rates, lactate may be a 'volume transmitter' of brain signals. According to some, lactate is a preferred fuel for brain metabolism. Immediately after brain activation, the rate of glycolysis exceeds oxidation, leading to net production of lactate. At physical rest, there is a net efflux of lactate from the brain into the blood stream. But when blood lactate levels rise, such as in physical exercise, there is net influx of lactate from blood to brain, where the lactate is used for energy production and myelin formation. Lactatebinds to the lactate receptor GPR81 aka hydroxycarboxylic acid receptor (HCAR1) on brain cells and cerebral blood vessels, and regulates the levels of cAMP. The localization and function of HCAR1 and the three MCTs (MCT1, MCT2, and MCT4) expressed in brain constitute the focus of this review. They are possible targets for new therapeutic drugs and interventions. The author proposes that lactate actions in the brain through MCTs and the lactate receptor underlie part of the favorable effects on the brain resulting from physical exercise.

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Monocarboxylate transport matters. Bergersen LH, Eid T. N Engl J Med. 371:1931-1932, 2014. 

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Effects of high- versus low-intensity resistance training on recovery after ACL-reconstruction. Beyer N. BioMed Research International. 278512, 2014.

Abstract:

Persistent weakness is a common problem after anterior cruciate ligament- (ACL-) reconstruction. This study investigated the effects of high-intensity (HRT) versus low-intensity (LRT) resistance training on leg extensor power and recovery of knee function after ACL-reconstruction. 31 males and 19 females were randomized to HRT (n = 24) or LRT (n = 26) from week 8-20 after ACL-reconstruction. Leg extensor power, joint laxity, and self-reported knee function were measured before and 7, 14, and 20 weeks after surgery. Hop tests were assessed before and after 20 weeks.

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Intra-rater test-retest reliability and agreement of hip and thigh muscle strength, muscle power and functional performance measures in patients with osteoarthritis of the hip. Bieler T, Magnusson SP, Kjaer M, Beyer N. Journal of Rehabilitation Medicine. 4; 46(10):997-1005, 2014.

Abstract:

To investigate the reliability and agreement of measures of lower extremity muscle strength, power and functional performance inpatients with hip osteoarthritis at different time intervals, and to compare these with the same measures in healthy peers. Intra-rater test-retest separated by 1, 2, or 2.5 weeks in patients, and 1 week in healthy peers. Patients with hip osteoarthritis (age range 61-83 years) with 1 (n = 37), 2 (n = 35), or 2.5 weeks (n = 15) between tests, and 35 healthy peers (age range 63-82 years). Maximal isometric hip and thigh strength, leg extensor power, and functional performance (8-foot Up & Go, stair climbing, chair stand and 6-min walk) were measured in patients, and quadriceps strength, leg extensor power and functional performance were measured in healthy peers. Systematic error, reliability and agreement were calculated.

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Significant gender difference in serum levels of fibroblast growth factor 21 in Danish Children and adolescents. Bieler T, Sobol N, Andersen L, Kiel P, Løfholm P, Aagaard P, Magnusson SP, Krogsgaard M, Bisgaard A, Sørensen K, Johannsen TH, Helge JW, Andersson AM, Juul A. Int J Pediatr Endocrinol. 2014(1): 7, 2014.

Abstract:

Fibroblast Growth Factor 21 (FGF21) is a novel metabolic factor with effect on glucose and lipid metabolism, and shown to be elevated in diseases related to metabolic syndrome. Due to the increasing frequency of metabolic syndrome in the pediatric population, and as FGF21 studies in children are limited, we investigated baseline serum levels of FGF21 in healthy children during an oral glucose tolerance test. A total of 179 children and adolescents from the COPENHAGEN Puberty Study were included. An OGTT with glucose and insulin measurements, a dual energy X-ray absorptiometry (DXA) scan and a clinical examination including pubertal staging were done on all subjects.Serum levels of FGF21, adiponectin, and leptin were determined by immunoassays at baseline.

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The dissolution of double Holliday junctions. Bizard AH, Hickson ID. Cold Spring Harbor Perspectives in Biology. 6:a016477, 2014.

Abstract:

Double Holliday junctions (dHJS) are important intermediates of homologous recombination. The separate junctions can each be cleaved by DNAstructure-selective endonucleases known as Holliday junction resolvases. Alternatively, double Holliday junctions can be processed by a reaction known as "double Holliday junction dissolution." This reaction requires the cooperative action of a so-called "dissolvasome" comprising a Hollidayjunction branch migration enzyme (Sgs1/BLM RecQ helicase) and a type IA topoisomerase (Top3/TopoIIIα) in complex with its OB (oligonucleotide/oligosaccharide binding) fold containing accessory factor (Rmi1). This review details our current knowledge of the dissolutionprocess and the players involved in catalyzing this mechanistically complex means of completing homologous recombination reactions.

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Structural and mechanistic insight into Holliday junction dissolution by topoisomerase IIIa and RMI1. Bocquet N, Bizard AH, Abdulrahman W, Larsen NB, Faty M, Cavadini I, Bunker R, Kowalczykowski SC, Cejka P, Hickson ID, Thomä N. Nature Struct. Molec. Biol. 21: 261-268, 2014.

Abstract:

Repair of DNA double-strand breaks via homologous recombination can produce double Holliday junctions (dHJs) that require enzymatic separation. Topoisomerase IIIα (TopIIIα) together with RMI1 disentangles the final hemicatenane intermediate obtained once dHJs have converged. How binding of RMI1 to TopIIIα influences it to behave as a hemicatenane dissolvase, rather than as an enzyme that relaxes DNA topology, is unknown. Here, we present the crystal structure of human TopIIIα complexed to the first oligonucleotide-binding domain (OB fold) of RMI1. TopIII assumes a toroidal type 1A topoisomerase fold. RMI1 attaches to the edge of the gate in TopIIIα through which DNA passes. RMI1 projects a 23-residue loop into the TopIIIα gate, thereby influencing the dynamics of its opening and closing. Our results provide a mechanistic rationale for how RMI1 stabilizes TopIIIα-gate opening to enable dissolution and illustrate how binding partners modulate topoisomerase function.

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Effect of growth hormone on aging connective tissue in muscle and tendon: gene expression, morphology, and function following immobilization and rehabilitation. Boesen AP, Dideriksen K, Couppé C, Magnusson SP, Schjerling P, Boesen M, Aagaard P, Kjaer M, Langberg H. Journal of Applied Physiology. 116:192-203, 2014.

Abstract:

It is unknown whether loss in musculotendinous tissue during inactivity can be counteracted by growth hormone (GH), and whether GH acceleraterehabilitation in aging individuals. Elderly men (65-75 yr; n = 12) had one leg immobilized 2 wk followed by 6 wk of retraining and were randomly assigned to daily injections of recombinant GH (rhGH; n = 6) or placebo (Plc; n = 6). Cross-sectional area (CSA), muscle strength (MVC), and biomechanical properties of m. quadriceps and patellar tendon were determined. Muscle and tendon biopsies were analyzed for gene expressions (mRNA) of collagen (COL1A1/3A1) and insulin-like growth factors (IGF-1Ea/Ec). Fibril morphology was analyzed by transmission electron microscope (TEM). In tendon, CSA and biomechanical properties did not change following immobilization, but an increase in CSA was found after 6 wk of rehabilitation in both groups. The changes were more pronounced when GH was injected. Furthermore, tendon stiffness increased in the GH group. Muscle CSA declined after immobilization in the Plc but not in the GH group. Muscle CSA increased during retraining, with a significantly larger increase in the GH group compared with the Plc group. Both a time and a group effect were seen for IGF-1Ea/Ec and COL1A1/3A1 mRNAexpression in muscle, with a difference between GH and Plc. IGF-1Ea/Ec and COL-1A1/3A1 mRNA expression increased in muscle followingimmobilization and retraining in subjects receiving GH, whereas an increase in IGF-1Ec mRNA expression was seen in the Plc group only after retraining. In conclusion, in elderly humans, GH seems to have a matrix stabilizing effect during inactivity and rehabilitation by stimulating collagenexpression in the musculotendinous tissue and increasing tendon CSA and stiffness.

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Low-intensity training increases peak arm VO2 by enhancing both convective and diffusive O2 delivery. Boushel R, Ara I, Gnaiger E, Helge JW, González-Alonso J, Munck-Andersen T, Sondergaard H, Damsgaard R, van Hall G, Saltin B, Calbet JA. Acta Physiol (Oxf). 2014 May; 211(1):122-34, 2014.

Abstract:

It is an ongoing discussion the extent to which oxygen delivery and oxygen extraction contribute to an increased muscle oxygen uptake during dynamic exercise. It has been proposed that local muscle factors including the capillary bed and mitochondrial oxidative capacity play a large role in prolonged low-intensity training of a small muscle group when the cardiac output capacity is not directly limiting. The purpose of this study was to investigate the relative roles of circulatory and muscle metabolic mechanisms by which prolonged low-intensity exercise training alters regional muscle VO2 . In nine healthy volunteers (seven males, two females), haemodynamic and metabolic responses to incremental arm cycling were measured by the Fick method and biopsy of the deltoid and triceps muscles before and after 42 days of skiing for 6 h day(-1) at 60% max heart rate.

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Mechanistic insight into the interaction of BLM helicase with intra-strand G-quadruplex structures. Chatterjee S, Zagelbaum J, Savitsky P, Huttner D, Sturzenegger A, Janscak P, Hickson ID, Gileadi O, Rothenberg E. Nature Communications . 5: 5556, 2014.

Abstract:

Bloom syndrome is an autosomal recessive disorder caused by mutations in the RecQ family helicase BLM that is associated with growth retardation and predisposition to cancer. BLM helicase has a high specificity for non-canonical G-quadruplex (G4) DNA structures, which are formed by G-rich DNA strands and play an important role in the maintenance of genomic integrity. Here we used single-molecule FRET to define the mechanism of interaction of BLM helicase with intra-stranded G4 structures. We show that the activity of BLM is substrate dependent, and highly regulated by a short-strand DNA (ssDNA) segment that separates the G4 motif from double-stranded DNA. We demonstrate cooperativity between the RQC and HRDC domains of BLM during binding and unfolding of the G4 structure, where the RQC domain interaction with G4 is stabilized by HRDC binding to ssDNA. We present a model that proposes a unique role for G4 structures in modulating the activity of DNA processing enzymes.

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Life-long endurance running is associated with reduced glycation and mechanical stress in connective tissue. Couppé C, Svensson RB, Kovanen V, Grosset JF, Karlsen A, Nielsen RH, Larsen J, Skovgaard D, Hansen M, Mackey A, Aagaard P, Kjær M, Magnusson SP.

Abstract:

Life-long regular endurance exercise is known to counteract the deterioration of cardiovascular and metabolic function and overall mortality. Yet it remains unknown if life-long regular endurance exercise can influence the connective tissue accumulation of advanced glycation end products (AGEs) that is associated with aging and lifestyle-related diseases. We therefore examined two groups of healthy elderly men: 15 master athletes (64 ± 4 years) who had been engaged in life-long endurance running and 12 old untrained (66 ± 4 years) together with two groups of healthy young men; ten young athletes matched for running distance (26 ± 4 years), and 12 young untrained (24 ± 3 years). AGE cross-links (pentosidine) of the patellar tendon were measured biochemically, and in the skin, it was assessed by a fluorometric method. In addition, we determined mechanicalproperties and microstructure of the patellar tendon. Life-long regular endurance runners (master athletes) had a 21 % lower AGE cross-link density compared to old untrained. Furthermore, both master athletes and young athletes displayed a thicker patellar tendon. These cross-sectional data suggest that life-long regular endurance running can partly counteract the aging process in connective tissue by reducing age-related accumulation of AGEs. This may not only benefit skin and tendon but also other long-lived protein tissues in the body. Furthermore, it appears that endurancerunning yields tendon tissue hypertrophy that may serve to lower the stress on the tendon and thereby reduce the risk of injury.

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Accuracy for MRI technique for measuring tendon cross-sectional area. Couppé C, Svensson RB, Sødring-Elbrønd V, Hansen P, Kjaer M, Magnusson SP. Clinical Physiology and Functional Imaging. 34: 237-41, 2014.

Abstract:

Magnetic resonance imaging (MRI) has commonly been applied to determine tendon cross-sectional area (CSA) and length either to measure structural changes or to normalize mechanical measurements to stress and strain. The ability to reproduce CSA measurements on MRI images has been reported, but the accuracy in relation to actual tendon dimensions has never been investigated. The purpose of this study was to comparetendon CSA measured by MRI with that measured in vitro with the mould casting technique. The knee of a horse was MRI-scanned with 1.5 and 3 tesla, and two examiners measured the patellar tendon CSA. Thereafter, the patellar tendon of the horse was completely dissected and embedded in an alginate cast. The CSA of the embedded tendon was measured directly by optical imaging of the cast impression. 1.5 tesla grey tendon CSA and 3 tesla grey tendon CSA were 16.5% and 13.2% lower than the mould tendon CSA, respectively. Also, 3 tesla tendon CSA, based on the red-green border on the National Institute of Health (NIH) colour scale, was lower than the mould tendon CSA by 2.8%. The typical error between examiners was below 2% for all the measured CSA. The typical error between examiners was below 2% for all the measured CSA. These data show thatmeasuring tendon CSA on the grey-scale MRI images is associated with an underestimation, but by optimizing the measurement using a 3 tesla MRIand the appropriate NIH colour scale, this underestimation could be reduced to 2.8% compared with the direct measurements on the mould.

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Three dimensional reconstruction of the human skeletal muscle mitochondrial network as a tool to assess mitochondrial content and structural organization. Dahl R, Larsen S, Dohlmann TL, Qvortrup K, Helge JW, Dela F, Prats C. Acta Physiol (Oxf). Accepted, 2014.

Abstract:
Mitochondria undergo continuous changes in shape as result of complex fusion and fission processes. The physiological relevance ofmitochondrial dynamics is still unclear. In the field of mitochondria bioenergetics, there is a need of tools to assess cell mitochondrial content. To develop a method to visualize mitochondrial networks in high resolution and assess mitochondrial volume. Confocal fluorescence microscopy imaging of mitochondrial network stains in human vastus lateralis single muscle fibres and focused ion beam/ scanning electron microscopy (FIB/SEM) imaging, combined with 3D reconstruction was used as a tool to analyse mitochondrialmorphology and measure mitochondrial fractional volume.

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Successful ageing: A historical overview and critical analysis of a successful concept. Bülow MH, Söderqvist T. J Aging Stud 31. 139-49, 2014.

Abstract:

Since the late 1980s, the concept of 'successful ageing' has set the frame for discourse about contemporary ageing research. Through an analysis of the reception to John W. Rowe and Robert L. Kahn's launch of the concept of 'successful ageing' in 1987, this article maps out the important themes and discussions that have emerged from the interdisciplinary field of ageing research. These include an emphasis on interdisciplinarity; the interaction between biology, psycho-social contexts and lifestyle choices; the experiences of elderly people; life-course perspectives; optimisation and prevention strategies; and the importance of individual, societal and scientific conceptualisations and understandings of ageing. By presenting an account of the recent historical uses, interpretations and critiques of the concept, the article unfolds the practical and normative complexities of 'successful ageing'.

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