Publikationer 2012 – Københavns Universitet

Videresend til en ven Resize Print Bookmark and Share

Sund Aldring > Publikationer > Videnskabelige publikationer > Publikationer 2012

 Publications 2012

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.

 

 Til toppenProgram 1a - Molecular and Cellular: Molecular Aging

14-3-3 checkpoint regulatory proteins interact specifically with DNA repair protein human exonuclease 1 (hEXO1) via a semi-con¬served motif. Andersen SD, Keijzers G, Rampakakis E, Engels K, Luhn P, El-Shemerly M, Nielsen FC, Du Y, May A, Bohr VA, Ferrari S, Zannis-Hadjopoulos M, Fu H, Rasmussen LJ. DNA Repair 11: 267-277, 2012. 

We demonstrate direct and robust interaction between hEXO1 and six of the seven 14-3-3 isoforms in vitro, suggestive of a novel protein interaction network between DNA repair and cell cycle control. Binding experiments reveal weak affinity of the more selective isoform 14-3-3σ but both 14-3-3 isoforms η and σ significantly stimulate hEXO1 activity, indicating that these regulatory proteins exert a common regulation mode on hEXO1. Results demonstrate that binding involves the phosphorable amino acid S746 in hEXO1 and most likely a second unidentified binding motif. 14-3-3 associations do not appear to directly influence hEXO1 in vitro nuclease activity or in vitro DNA replication initiation.

See full abstract

A novel anti-recombinase gains PARIty. Mankouri HW, Chu W-K, Hickson ID. Molecular Cell 45: 6-7, 2012. 

In this issue, Moldovan et al. (2012) report the identification of PARI, a putative human ortholog of the yeast Srs2 protein, which potentially regulates homologous recombination repair via its ability to disrupt the function of RAD51.

see full abstract

A small molecule inhibitor of the BLM helicase modulates chromosome stability in human cells. Nguyen GH, Dexheimer TS, Rosenthal AS, Chu W-K, Singh DK, Mosedale G, Bachrati CZ, Schultz L, Sakurai M, Savitsky P, Abu M, McHugh PJ, Bohr VA, Harris CC, Jadhav A, Gileadi O, Maloney DJ, Simeonov A, and Hickson ID. Chem Biol. 2013 Jan 24;20(1):55-62. doi: 10.1016/j.chembiol.2012.10.016. 

In order to be able to acutely disable BLM function in cells, we undertook a high throughput screen of a chemical compound library for small molecule inhibitors of BLM. We present ML216, a potent inhibitor of the DNA unwinding activity of BLM. ML216 shows cell-based activity and can induce sister chromatid exchanges, enhance the toxicity of aphidicolin, and exert antiproliferative activity in cells expressing BLM, but not those lacking BLM. These data indicate that ML216 shows strong selectivity for BLM in cultured cells. We discuss the potential utility of such a BLM-targeting compound as an anticancer agent.

see full abstract

Altered expression of brain monocarboxylate transporter 1 in models of temporal lobe epilepsy. Lauritzen F, Perez EL, Melillo ER, Roh JM, Zaveri HP, Lee TSW, Wang Y, Bergersen LH, Eid T. Neurobiol Dis 45(1): 165-176, 2012. 

We recently reported that MCT1 is deficient on microvessels in the epileptogenic hippocampal formation in patients with medication-refractory temporal lobe epilepsy (TLE). To further define the role of MCT1 in the pathophysiology of TLE, we used immunohistochemistry and stereological analysis to localize and quantify the transporter in the hippocampal formation in three novel and highly relevant rat models of TLE and in nonepileptic control animals. One model utilizes methionine sulfoximine to induce brain glutamine synthetase deficiency and recurrent limbic seizures, while two models employ an episode of perforant pathway stimulation to cause epilepsy. MCT1 was lost on microvessels and upregulated on astrocytes in the hippocampal formation in all models of TLE...

see full abstract

see full article

Base excision repair efficiency and mechanism in nuclear extracts are influenced by the ratio between volume of nuclear extraction buffer and nuclei-Implications for comparative studies. Akbari M, Krokan H. Muta¬tion Research 736: 33-38, 2012. 

Here we have examined BER activity of nuclear cell extracts from HeLa cells, using as substrate a circular DNA molecule with either uracil or an AP-site in a defined position. We show that BER activity of nuclear extracts from the same batch of cells varies inversely with the volume of nuclear extraction buffer relative to nuclei volume, in spite of identical protein concentrations in the BER assay mixture. Surprisingly, the uracil-DNA glycosylase activity (mainly UNG2), but not amount of UNG2, also correlated negatively with the volume of extraction buffer. These studies demonstrate that the method for preparation of nuclear extract is an important factor to consider for in vitro BER analysis and conditions used in comparative studies must be carefully worked out.

See full abstract  

BLM and RMI1 alleviate RPA inhibition of Topo IIIa decatenase activity. Yang J, Bachrati CZ, Hickson ID, Brown GW: PLoS One 7: e41208, 2012. 

RPA is a single-stranded DNA binding protein that physically associates with the BLM complex. RPA stimulates BLM helicase activity as well as the double Holliday junction dissolution activity of the BLM-topoisomerase IIIα complex. We investigated the effect of RPA on the ssDNA decatenase activity of topoisomerase IIIα. We found that RPA and other ssDNA binding proteins inhibit decatenation by topoisomerase IIIα.

See full abstract

See full text

Cockayne syndrome group B protein prevents mitochondrial stress and promotes autophagy. Scheibye-Knudsen M, Ramamoorthy M, Sykora P, Maynard S, Lin P-C, Minor RK, Wilson III DM, Cooper M, Spencer R, de Cabo R, Croteau DL, Bohr VA: J Exp Med. 209(4): 855-869, 2012. 

Cockayne syndrome (CS) is a devastating autosomal recessive disease characterized by neurodegeneration, cachexia, and accelerated aging. 80% of the cases are caused by mutations in the CS complementation group B (CSB) gene known to be involved in DNA repair and transcription. Recent evidence indicates that CSB is present in mitochondria, where it associates with mitochondrial DNA (mtDNA). We report an increase in metabolism in the CSB(m/m) mouse model and CSB-deficient cells. Mitochondrial content is increased in CSB-deficient cells, whereas autophagy is down-regulated, presumably as a result of defects in the recruitment of P62 and mitochondrial ubiquitination...

See full abstract

Collaborative interplay between FGF-2 and VEGF-C promotes lymphangiogenesis and metastasis. Cao R, Ji H, Feng N, Zhang Y, Yang X, Andersson P, Sun Y, Tritsaris K, Hansen AJ, Dissing S Cao Y. Proc Natl Acad Sci. 109(39): 15894-9, 2012. 

Here we show that FGF-2 and VEGF-C, two lymphangiogenic factors, collaboratively promote angiogenesis and lymphangiogenesis in the tumor microenvironment, leading to widespread pulmonary and lymph-node metastases. Coimplantation of dual factors in the mouse cornea resulted in additive angiogenesis and lymphangiogenesis.

See full abstract

See full article

Determining the functional significance of mismatch repair gene missense variants using biochemical and cellular assays. Heinen CD, Rasmussen LJ: Hereditary Cancer in Clin Prac. 10: 9, 2012. 

The ability to reconstitute the MMR reaction in vitro has provided an important experimental tool for studying the functional consequences of VUS. However, beyond this repair assay, a number of other experimental methods have been developed that allow us to test the effect of a VUS on discrete biochemical steps or other aspects of MMR function. Here, we describe some of these assays along with the challenges of using such assays to determine the functional consequences of MMR VUS which, in turn, can provide valuable insight into their clinical significance...

see full abstract

see full article

Evaluation of MLH1 I219V Polymorphism in Unrelated South American Individuals Suspected of Having Lynch Syndrome.Dominguez Valentin M, Carneiro Da Silva F, Monteiro Santos EM, Da Silva SD, de Oliveira Ferreira F, Aguiar Junior S, Gomy I, Vaccaro C, Redal MA, Valle AD, Sarroca C, Rasmussen LJ, Carraro DM, Rossi BM. Anticancer Res. 32: 4347-4351, 2012. 

Some single-nucleotide polymorphisms are associated with higher risk of colorectal cancer development and are suggested to explain part of the genetic contribution to Lynch syndrome. Aim: To evaluate the mutL homolog 1 (MLH1) I219V polymorphism in 124 unrelated South American individuals suspected of having Lynch syndrome, based on frequency, association with pathogenic MLH1 and mutS homolog 2 (MSH2) mutation and clinical features. DNA was obtained from peripheral blood and polymerase chain reaction (PCR) was performed, followed by direct sequencing.

See full abstract

Evidence for astrocytes as a potential source of the glutamate excess in temporal lobe epilepsy. Perez EL, Lauritzen F, Wang Y, Lee TS, Kang D, Zaveri HP, Chaudhry FA, Ottersen OP, Bergersen LH, Eid T. Neurobiol Dis. 47(3): 331-337, 2012. 

Increased extracellular brain glutamate has been implicated in the pathophysiology of human refractory temporal lobe epilepsy (TLE), but the cause of the excessive glutamate is unknown. Prior studies by us and others have shown that the glutamate degrading enzyme glutamine synthetase (GS) is deficient in astrocytes in the epileptogenic hippocampal formation in a subset of patients with TLE. We have postulated that the loss of GS in TLE leads to increased glutamate in astrocytes with elevated concentrations of extracellular glutamate and recurrent seizures as the ultimate end-points. Here we test the hypothesis that the deficiency in GS leads to increased glutamate in astrocytes. Rats were chronically infused with methionine sulfoximine (MSO, n=4) into the hippocampal formation to induce GS deficiency and recurrent seizures...

see full abstract

Expression of the vitamin D metabolizing enzyme CYP24A1 at the annulus of human spermatozoa may serve as a novel marker of semen quality. Blomberg Jensen M, Jørgensen A, Nielsen JE, Bjerrum PJ, Skalkam M, Petersen JH, Egeberg DL, Bangsbøll S, Andersen AN, Skakkebaek NE, Juul A, Rajpert-De Meyts E, Dissing S, Leffers H, Jørgensen N. Int J Androl. 35(4): 499-510, 2012. 

Here, we investigated if CYP24A1 expression serves as a marker for VD metabolism in spermatozoa, and whether CYP24A1 expression was associated with semen quality. We included 130 men (53 healthy young volunteers and 77 subfertile men) for semen analysis and immunocytochemical (ICC) detection of CYP24A1. Another 40 men (22 young, 18 subfertile) were tested for in vitro effects of 1,25(OH)(2)D(3) on intracellular calcium concentration ([Ca(2+)](i)) and sperm motility. Double ICC staining showed that CYP24A1 and VDR were either concomitantly expressed or absent in 80% of the spermatozoa from young men. The median number of CYP24A1-expressing spermatozoa was 1% in subfertile men and thus significantly (p < 0.0005) lower than 25% in spermatozoa from young men.

See full abstract

FBH1 co-operates with MUS81 in inducing DNA double-strand breaks and cell death following replication stress. Fugger K, Chu W-K, Haahr P, Kousholt AN, Beck H, Payne MJ, Hanada K, Hickson ID, Sørensen CS: Nat Commun. 2013;4:1423. 

Here, we identify a key role for the FBH1 helicase in mediating DNA double-strand break formation following replication inhibition. We show that FBH1-deficient cells are resistant to killing by hydroxyurea, and exhibit impaired activation of the pro-apoptotic factor p53, consistent with decreased DNA double-strand break formation. We also show that FBH1 through its helicase activity co-operates with the MUS81 nuclease in promoting the endonucleolytic DNA cleavage following prolonged replication stress...

see full abstract

Functional characteri¬zation of MLH1 missense variants identified in Lynch Syndrome patients.Andersen SD, Liberti SE, Lützen A, Drost M, Bernstein I, Nilbert M, Dominguez M, Nyström M, Hansen TVO, Christoffersen JW, Jäger AC, de Wind N, Nielsen FC, Tørring PM and Rasmussen LJ. Human Mutat 33: 1647-1655, 2012. 

We have examined the functionality of a panel of MLH1 missense mutations found in LS families, by testing the variant proteins in functional assays, addressing subcellular localization, and protein-protein interaction with the dimer partner PMS2 and the MMR-associated exonuclease 1. We show that a significant proportion of examined variant proteins have functional defects in either subcellular localization or protein-protein interactions, which is suspected to lead to the cancer phenotype observed in patients. Moreover, the obtained results correlate well with reported MMR activity and with in silico analysis for a majority of the variants.

See full abstract

Genome wide screens for expressed hypothetical proteins. Desler C, Durhuus JA, Rasmussen LJ. Functional Genomics, second edition, Methods in Molecular Biology 815: 25-38, 2012. 

A hypothetical protein (HP) is defined as a protein that is predicted to be expressed from an open reading frame, but for which there is no experimental evidence of translation. HPs constitute a substantial fraction of proteomes of human as well as of other organisms. With the general belief that the majority of HPs are the product of pseudogenes, it is essential to have a tool with the ability of pinpointing the minority of HPs with a high probability of being expressed.

See full abstract

Helicobacter pylori infection affects mitochondrial function and DNA repair, thus, mediating genetic instability in gastric cells. Machado AM, Desler C, Bøggild S, Strickertsson JA, Friis-Hansen L, Figueiredo C, Seruca R, Rasmussen LJ. Mech. Aging Dev. In press, 2012.

The helicase and ATPase activities of RECQL4 are compromised by mutations reported in three human patients.Jensen MB, Dunn C, Keijzers G, Kulikowicz T, Rasmussen LJ, Croteau DL, Bohr VA. Aging. Aging (Albany NY). 2012 Nov;4(11):790-802. 

RECQL4 is one of five members of the human RecQ helicase family, and is implicated in three syndromes displaying accelerating aging, developmental abnormalities and a predisposition to cancer. In this study, we purified three variants of RECQL4 carrying previously reported patient mutations. These three mutant proteins were analyzed for the known biochemical activities of RECQL4: DNA binding, unwinding of duplex DNA, ATP hydrolysis and annealing of simplex DNA...

see full abstract

see full text

Hippocampal adult neurogenesis is maintained by Neil3-dependent repair of oxidative DNA lesions in neural progenitor cells. Regnell CE, Hildrestrand GA, Sejersted Y, Medin T, Moldestad O, Rolseth V, Krokeide SZ, Suganthan R, Luna L, Bjørås M, Bergersen LH. Cell Rep 2: 503-510, 2012. 

Accumulation of oxidative DNA damage has been proposed as a potential cause of age-related cognitive decline. The major pathway for removal of oxidative DNA base lesions is base excision repair, which is initiated by DNA glycosylases. In mice, Neil3 is the main DNA glycosylase for repair of hydantoin lesions in single-stranded DNA of neural stem/progenitor cells, promoting neurogenesis. Adult neurogenesis is crucial for maintenance of hippocampus-dependent functions involved in behavior. Herein, behavioral studies reveal learning and memory deficits and reduced anxiety-like behavior in Neil3(-/-) mice...

See full abstract

Is lactate a volume transmitter of meta¬bolic states in the brain? Bergersen LH, Gjedde A. Front Neuroenergetics 4: 1-6. doi: 10.3389/fnene.2012.00005, 2012. 

We present the perspective that lactate is a volume transmitter of cellular signals in brain that acutely and chronically regulate the energy metabolism of large neuronal ensembles. From this perspective, we interpret recent evidence to mean that lactate transmission serves the maintenance of network metabolism by two different mechanisms, one by regulating the formation of cAMP via the lactate receptor GPR81, the other by adjusting the NADH/NAD(+) redox ratios, both linked to the maintenance of brain energy turnover and possibly cerebral blood flow. The role of lactate as mediator of metabolic information rather than metabolic substrate answers a number of questions raised by the controversial oxidativeness of astrocytic metabolism and its contribution to neuronal function.

See full abstract

Is there a link between Mitochondrial reserve respiratory capacity and aging? Desler C, Hansen TL, Frederiksen JB, Marcker ML, Singh KK, Rasmussen LJ. J. Aging Res. 2012: 192503. Epub 2012 Jun 5, 2012. 

Oxidative phosphorylation is an indispensable resource of ATP in tissues with high requirement of energy. If the ATP demand is not met, studies suggest that this will lead to senescence and cell death in the affected tissue. The term reserve respiratory capacity or spare respiratory capacity is used to describe the amount of extra ATP that can be produced by oxidative phosphorylation in case of a sudden increase in energy demand. Depletion of the reserve respiratory capacity has been related to a range of pathologies affecting high energy requiring tissues. During aging of an organism, and as a result of mitochondrial dysfunctions, the efficiency of oxidative phosphorylation declines.

See full abstract

Mitochondria In Biology and Medicine. Desler C, Rasmussen LJ. Mito¬chondrion 12: 472-476, 2012. 

Since 1959, the understanding of mitochondrial cytopathies has evolved immensely and mitochondrial cytopathies are now known to be the largest group of metabolic diseases and to be resulting in a wide variety of pathologies. "Mitochondria in Biology and Medicine" was the title of the first annual conference of Society of Mitochondrial Research and Medicine - India. The conference featured talks from internationally renowned scientists within the field of mitochondrial research and offered both students and fellow researchers a comprehensive update to the newest research within the field. This paper summarizes key outcomes of the presentations.

See full abstract

Medicin og mundtørhed. Føhns CL, Pedersen AML, Andersen SE: Månedsskrift for Praktisk Lægegerning, 10 (90): 835-38, 2012. 

Xerostomi (følelsen af mundtørhed) er den hyppigste medicinbivirkning i munden. I denne artikel er formålet at henlede opmærksomheden på lægemidler, som kan give xerostomi og nedsat spytsekretion samt at oplyse om forebyggende tiltag.

Non-genomic effects of vitamin D in hu¬man spermatozoa. Blomberg Jensen M, Dissing S. Steroids 77(10): 903-9, 2012. 

The spectrum for vitamin D (VD) mediated effects has expanded in recent years. Activated VD (1,25(OH)(2)D(3)) binds to the VD receptor (VDR) and mediates non-genomic effects through the alternative ligand binding-pocket (VDR-ap) or regulates gene transcription through the genomic binding-pocket. VDR and VD-metabolizing enzymes are expressed in human testis, male reproductive tract and mature spermatozoa, and VD is considered important for male reproduction. Expression of the VD-inactivating enzyme CYP24A1 at the annulus of human spermatozoa distinguish normal and infertile men with high specificity, and CYP24A1 expression is positively correlated with all semen variables and suggested as a marker for both semen quality and VD responsiveness.

See full abstract

Orale manifestationer ved Sjögrens syndrom og reumatoid artritis. Pedersen AML, Poulsen AH. Tandlægebladet 116(3): 182-88, 2012. Same article published in: Tandläkertidningen 2012, The Norwegian Dental Journal 122(2): 122-8, 2012 and the Finnish Dental Journal 2012.

Oral manifestations in Sjögrens syndrome and rheumatoid arthritis Sjögren’s syndrome (SS) and rheumatoid arthritis (RA) are the most common chronic, systemic, inflammatory autoimmune connective tissue disorders. They share several clinical and pathogenetic characteristics and both affect the oral cavity. SS is characterised by lymphocytic infiltration of the exocrine glands, in particular the lacrimal and salivary glands, leading to glandular hypofunction and symptoms of oral and ocular dryness. Impaired saliva secretion increases the risk of oral diseases like caries and candidal infections. SS may occur on its own (primary SS) or in association with another inflammatory connective tissue disease, most frequently RA (termed secondary SS). RA is characterised by inflammation of the synovium (synovitis), leading to destruction of articular cartilage and bone, atrophy of muscles, osteoporosis and joint deformities. Several studies have shown that periodontal disease is more prevalent in patients with RA than in the general population. The mechanisms behind the association between RA and periodontitis are not yet clarified, but may be related to mutual bacterial, inflammatory and genetic factors.

See full text (danish)

Oxidative damage to DNA by diesel exhaust particle exposure in co-cultures of human lung epithelial cells and macrophages. Jantzen K, Roursgaard M, Desler C, Loft S, Rasmussen LJ, Peter Møller: Mutagenesis 27: 693-701, 2012.

We investigated the effect of co-culturing type II lung epithelial A549 cells with macrophages upon treatment with standard reference DEPs, SRM2975 and SRM1650b. The exposure to DEPs did not affect the colony-forming ability of A549 cells in co-culture with THP-1a cells. The DEPs generated DNA strand breaks and oxidatively damaged DNA, measured using the alkaline comet assay as formamidopyrimidine-DNA glycosylase or oxoguanine DNA glycosylase (hOGG1) sensitive sites, in mono-cultures of A549 or THP-1a and co-cultures of A549 and THP-1a cells. The strongest genotoxic effects were observed in A549 mono-cultures and SRM2975 was more potent than SRM1650b.

see full abstract

Oxygen consumption and blood flow coupling in human motor cortex during intense finger tapping: implication for a role of lactate. Vafaee MS, Vang K, Bergersen LH, Gjedde A. J Cereb Blood Flow Metab. 32: 1859-1868, 2012. 

Rates of cerebral blood flow (CBF) and glucose consumption (CMR(glc)) rise in cerebral cortex during continuous stimulation, while the oxygen-glucose index (OGI) declines as an index of mismatched coupling of oxygen consumption (cerebral metabolic rate of oxygen-CMRO(2)) to CBF and CMR(glc). To test whether the mismatch reflects a specific role of aerobic glycolysis during functional brain activation, we determined CBF and CMRO(2) with positron emission tomography (PET) when 12 healthy volunteers executed finger-to-thumb apposition of the right hand...

See full abstract

Pathological assessment of mismatch repair gene variants in Lynch syndrome: past, present and future. Rasmussen LJ, Heinen CD, Royer-Pokora B, Drost M, Tavtigian S, Hofstra RMW, de Wind N. Human Mutat. 33: 1617-25. 2012. 

Lynch syndrome (LS) is caused by germline mutations in DNA mismatch repair (MMR) genes and is the most prevalent hereditary colorectal cancer syndrome. A significant proportion of variants identified in MMR and other common cancer susceptibility genes are missense or noncoding changes whose consequences for pathogenicity cannot be easily interpreted. Such variants are designated as "variants of uncertain significance" (VUS). Management of LS can be significantly improved by identifying individuals who carry a pathogenic variant and thus benefit from screening, preventive, and therapeutic measures...

See full abstract

Point-of-care diagnostics in oral medicine: salivary biomarkers potential and limitations. Pedersen AML, Vissink A, Proctor G. New Advances in Oral Medicine 2, 2012.

Rapid cell-free assay to test the activity of Lynch Syndrome-associated MSH2 and MSH6 variants suggests absence of pathogenicity in MSH6 variants. Drost M, Zonneveld JBM, van Hees S, Rasmussen LJ, Hofstra RMW, de Wind NA: Human Mutat. 33: 488-494, 2012. 

Here we present a rapid cell-free assay to investigate MMR activity of MSH2 or MSH6 VUS. We used this assay to analyze a series of MSH2 and MSH6 VUS, selected from the Leiden Open Variation Database. Whereas a significant fraction of the MSH2 VUS has lost MMR activity, suggesting pathogenicity, the large majority of the MSH6 VUS appears MMR proficient. We anticipate that this assay will be an important tool in the development of a comprehensive and widely applicable diagnostic procedure for LS-associated VUS

See full abstract

RecQ helicases – conserved guardians of genome integrity. Larsen NB, Hickson ID. Adv Exp Med Biol. 2013;767:161-84. 

In this review, we focus on the roles of BLM and its S. cerevisiae homologue, Sgs1, in genome maintenance. BLM/Sgs1 has been shown to play a critical role in homologous recombination at multiple steps, including end-resection, displacement loop formation, branch migration and double Holliday junction dissolution. In addition, recent evidence has revealed a role for BLM/Sgs1 in the stabilisation and repair of replication forks damaged during a perturbed S-phase. Finally BLM also plays a role in the suppression and/or resolution of ultra-fine anaphase DNA bridges that form between sister-chromatids during mitosis.

see full abstract

RECQL4 localizes to mitochondria and preserves mitochondrial DNA integrity. Croteau DL, Rossi ML, Canugovi C, Tian J, Sykora P, Ramamoorthy M, Wang ZM, Singh DK, Akbari M, Kasiviswanathan R, Copeland WC, Bohr VA. Aging Cell 11(3): 456-66, 2012. 

Here, we used microscopy to visualize RECQL4 in mitochondria. Fractionation of human and mouse cells also showed that RECQL4 was present in mitochondria. Q-PCR amplification of mitochondrial DNA demonstrated that mtDNA damage accumulated in RECQL4-deficient cells. Microarray analysis suggested that mitochondrial bioenergetic pathways might be affected in RTS. Measurements of mitochondrial bioenergetics showed a reduction in the mitochondrial reserve capacity after lentiviral knockdown of RECQL4 in two different primary cell lines.

see full abstract

Redistribution of monocarboxylate transporter 2 on the surface of astrocytes in the human epileptogenic hippocampus. Lauritzen F, Heuser K, de Lanerolle NC, Lee TS, Spencer DD, Kim JH, Gjedde A, Eid T, Bergersen LH. Glia 60(7):1172-1181, 2012. 

Recently, we reported that the density of MCT1 protein is reduced on endothelial cells and increased on astrocyte plasma membranes in the hippocampal formation in patients with MTLE and in several animal models of the disorder. Because the perivascular astrocyte endfeet comprise an important part of the neurovascular unit, we now assessed the distribution of the MCT2 in hippocampal formations in TLE patients with (MTLE) or without hippocampal sclerosis (non-MTLE). Light microscopic immunohistochemistry revealed significantly less perivascular MCT2 immunoreactivity in the hippocampal formation in MTLE (n = 6) than in non-MTLE (n = 6) patients, and to a lesser degree in non-MTLE than in nonepilepsy patients (n = 4)...

see full abstract

Saliva and salivary biomarkers for primary Sjögren’s syndrome. A valid tool for diagnosing SS, for monitoring disease activity and prognosis, and for assessing treatment efficacy? Pedersen AML, Vissink A, Proctor G. New Advances in Oral Medicine 2, 2012

Rinholm JE, Bergersen LH: The wrap that feeds neuorns. Nature 487:435-436, 2012. 

Comment on Oligodendroglia metabolically support axons and contribute to neurodegeneration.

See full abstract

X-ray repair cross complementing protein 1 in base excision repair. Hanssen-Bauer A, Solvang-Garten K, Akbari A, Otterlei M. Int J Mol Sci. 2012 Dec 17;13(12)

 X-ray Repair Cross Complementing protein 1 (XRCC1) acts as a scaffolding protein in the converging base excision repair (BER) and single strand break repair (SSBR) pathways. XRCC1 also interacts with itself and rapidly accumulates at sites of DNA damage. XRCC1 can thus mediate the assembly of large multiprotein DNA repair complexes as well as facilitate the recruitment of DNA repair proteins to sites of DNA damage...

see full abstract

see full article

Ældres tand- og mundsundhed relateret til kostindtag og ernæringsstatus. Pedersen AML, Dynesen AW: Diætisten 117. 14-17, 2012.

 Program 1b - Molecular and Cellular: NeurobiologyTil toppen

Alterations of monocarboxylate transporter densities during hypoxia in brain and breast tumour cells. Cheng C, Jeppesen Edin NF, Lauritzen KH, Aspmodal I, Christoffersen S, Jian L, Rasmussen LJ, Pettersen EO, Xiaoqun G, Bergersen LH. Cel. Oncol. 35: 217-227. 2012. 

In order to identify differences in the capacity for lactate exchange, human T-47D breast cancer cells and human glioblastoma T98G cells were grown under 4 % or 20 % oxygen conditions and examined for MCT1, MCT2 and MCT4 expression on plasma membranes by quantitative post embedding immunogold electron microscopy. Whereas previous studies on MCT expression in tumours have recorded mRNA and protein levels in cell extracts, we examined concentrations of the proteins in the microvillous plasma membrane protrusions specialized for transmembrane transport.

See full abstract

See full article

Automatic detection of REM sleep in subjects without atonia. Kempfner J, Jennum P, Nikolic M, Christensen JA, Sorensen HB. Conf Proc IEEE Eng Med Biol Soc. 4242-5, 2012. doi: 10.1109/EMBC.2012.6346903. PubMed PMID: 23366864, 2012. 

In this study a full automatic REM sleep detector, using the EOG and EEG channels, is proposed. Based on statistical features, combined with subject specific feature scaling and post-processing of the classifier output, it was possible to obtain an mean accuracy of 0.96 with a mean sensitivity and specificity of 0.94 and 0.96 respectively.

see full abstract

Estimation of intersubject variability of cerebral blood flow measurements using MRI and positron emission tomography. Henriksen OM, Larsson HBW, Hansen AE, Grüner JM, Law I, Rostrup E. J Magn Reson Imaging, 35:1290-1299, 2012. 

PURPOSE: To investigate the within and between subject variability of quantitative cerebral blood flow (CBF) measurements in normal subjects using various MRI techniques and positron emission tomography (PET). MATERIALS AND METHODS: Repeated CBF measurements were performed in 17 healthy, young subjects using three different MRI techniques: arterial spin labeling (ASL), dynamic contrast enhanced T1 weighted perfusion MRI (DCE) and phase contrast mapping (PCM)...

see full abstract

Evaluation of novel algorithm embedded in a wearable sEMG device for seizure detec¬tion. Conradsen I, Beniczky S, Wolf P, Jennum P, Sorensen HB. Conf Proc IEEE Eng Med Biol Soc. 2048-51, 2012. doi: 10.1109/EMBC.2012.6346361. PubMed PMID: 23366322, 2012. 

We implemented a modified version of a previously published algorithm for detection of generalized tonic-clonic seizures into a prototype wireless surface electromyography (sEMG) recording device. The method was modified to require minimum computational load, and two parameters were trained on prior sEMG data recorded with the device. Along with the normal sEMG recording, the device is able to set an alarm whenever the implemented algorithm detects a seizure. These alarms are annotated in the data file along with the signal. The device was tested at the Epilepsy Monitoring Unit (EMU) at the Danish Epilepsy Center.

see full abstract

Health, social and economic consequences of neck injuries: a controlled national study evaluating societal effects on patients and their partners. Jennum P, Kjellberg J, Ibsen R, Bendix T. Spine (Phila Pa 1976). 2013 Mar 1;38(5):449-57. 

OBJECTIVE: The aim of this study was to estimate the direct and indirect costs of neck injuries, except fractures, in a national sample of patients and their spouses. METHODS: Using records from the Danish National Patient Registry 1998-2009, all patients with a diagnosis of neck injury and their spouses were identified and compared with randomly chosen controls matched for age, sex, geographical area, and civil status...

see full abstract

Health, social, and economic consequences of narcolepsy: a controlled national study evaluating the societal effect on patients and their partners. Jennum P, Ibsen R, Petersen ER, Knudsen S, Kjellberg J. Sleep Med. 13(8): 1086-93, 2012. 

Despite the fact that narcolepsy is a chronic disorder affecting younger people, there is insufficient information about its societal burden, time course, and familiar effect. We aimed to estimate the factual direct and indirect costs of narcolepsy patients and their families in a national sample using a controlled study design...

see full abstract

Mortality, health, social and economic consequences of amyotrophic lateral sclerosis: a controlled national study. Jennum P, Ibsen R, Pedersen SW, Kjellberg J. J Neurol. 2013 Mar;260(3):785-93. 

We aimed to estimate the factual direct and indirect costs of Amyotrophic lateral sclerosis in a national sample. Using records from the Danish National Patient Registry (1998-2009), 2,394 patients with ALS were identified and subsequently compared with 9,575 randomly chosen control subjects matched for age, gender and geographic area/civil status. Direct costs, including frequencies of primary and sector contacts and procedures, and medication from primary and secondary sectors, were obtained from the Danish Ministry of Health, the Danish Medicines Agency, and the National Health Security...

see full abstract

Multiscale Vision Model Highlights Spontaneous Glial Calcium Waves Recorded by 2-Photon Imaging in Brain Tissue. Brazhe A, Mathiesen C, Lauritzen M. Neuroimage. In press, 2012. 

Intercellular glial calcium waves (GCW) constitute a signaling pathway which can be visualized by fluorescence imaging of cytosolic Ca(2+) changes. Reliable detection of calcium waves in multiphoton imaging data is challenging because of low signal-to-noise ratio. We modified the multiscale vision model (MVM), originally employed to detect faint objects in astronomy data to process stacks of fluorescent images. We demonstrate that the MVM identified and characterized GCWs with much higher sensitivity and detail than pixel thresholding. Origins of GCWs were often associated with prolonged secondary Ca(2+) elevations.

See full abstract

Recommendations to improve imaging and analysis of brain lesion load and atrophy in longitudinal studies of multiple sclerosis. Vrenken H, Jenkinson M, Horsfield MA, Battaglini M, van Schijndel RA, Rostrup E, Geurts JJG, Fisher E, Zijdenbos A, Ashburner J, Miller DH, Filippi M, Fazekas F, Rovaris M, Rovira A, Barkhof F, De Stefano N: Journal of Neurology, 21, doi:10.1007/s00415-012-6762-5, 2012. 

Focal lesions and brain atrophy are the most extensively studied aspects of multiple sclerosis (MS), but the image acquisition and analysis techniques used can be further improved, especially those for studying within-patient changes of lesion load and atrophy longitudinally. Improved accuracy and sensitivity will reduce the numbers of patients required to detect a given treatment effect in a trial, and ultimately, will allow reliable characterization of individual patients for personalized treatment...

See full abstract

Separation of Parkinson's patients in early and mature stages from control subjects using one EOG channel. Christensen JA, Frandsen R, Kempfner J, Arvastson L, Christensen SR, Jennum P, Sorensen HB. Conf Proc IEEE Eng Med Biol Soc. 2941-4, 2012. doi: 10.1109/EMBC. 2012.6346580. PubMed PMID: 23366541, 2012. 

In this study, polysomnographic left side EOG signals from ten control subjects, ten iRBD patients and ten Parkinson's patients were decomposed in time and frequency using wavelet transformation. A total of 28 features were computed as the means and standard deviations in energy measures from different reconstructed detail subbands across all sleep epochs during a whole night of sleep. A subset of features was chosen based on a cross validated Shrunken Centroids Regularized Discriminant Analysis, where the controls were treated as one group and the patients as another.

See full abstract

Spontaneous Calcium Waves in Bergman Glia Increase with Age and Hypoxia and May Reduce Tissue Oxygen. Mathiesen C, Brazhe A, Thomsen K, Lauritzen, M. J Cereb Blood Flow Metab. 2013 Feb;33(2):161-9. 

Glial calcium (Ca(2+)) waves constitute a means to spread signals between glial cells and to neighboring neurons and blood vessels. These waves occur spontaneously in Bergmann glia (BG) of the mouse cerebellar cortex in vivo. Here, we tested three hypotheses: (1) aging and reduced blood oxygen saturation alters wave activity; (2) glial Ca(2+) waves change cerebral oxygen metabolism; and (3) neuronal and glial wave activity is correlated. We used two-photon microscopy in the cerebellar cortexes of adult (8- to 15-week-old) and aging (48- to 80-week-old) ketamine-anesthetized mice after bolus loading with OGB-1/AM and SR101. We report that the occurrence of spontaneous waves is 20 times more frequent in the cerebellar cortex of aging as compared with adult mice, which correlated with a reduction in resting brain oxygen tension...

see full abstract

The hemodynamic signal: reflecting neuronal inhibition or excitation? Lauritzen M, Mathiesen C, Thomsen KJ. Neuroimage, 15;62(2): 1040-50, 2012. 

Brain's electrical activity correlates strongly to changes in cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen (CMRO(2)). Subthreshold synaptic processes correlate better than the spike rates of principal neurons to CBF, CMRO(2) and positive BOLD signals. Stimulation-induced rises in CMRO(2) are controlled by the ATP turnover, which depends on the energy used to fuel the Na,K-ATPase to reestablish ionic gradients, while stimulation-induced CBF responses to a large extent are controlled by mechanisms that depend on Ca(2+) rises in neurons and astrocytes...

see full abstract

Negative BOLD signal changes in ipsilateral primary somatosensory cortex are associated with perfusion decreases and behavioral evidence for functional inhibition. Schäfer K, Blankenburg F, Kupers R, Grüner JM, Law I, Lauritzen M, Larsson HB. Neuroimage 15;59(4): 3119-27, 2012. 

We used functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) to study the negative blood oxygenation level dependent (BOLD) signal and its underlying blood flow changes in healthy human subjects. This was combined with psychophysiological measurements to test that the negative BOLD signal is associated with functional inhibition. Electrical stimulation of the median nerve at 7 Hz evoked robust negative BOLD signals in the primary somatosensory cortex (SI) ipsilateral to stimulation, and positive BOLD signals in contralateral SI...

See full abstract

Prognostic value of periodic electroencephalographic discharges for neurological patients with profound disturbances of consciousness. Pedersen GL, Rasmussen SB, Gyllenborg J, Benedek K, Lauritzen M.Clin Neurophysiol. 2013 Jan;124(1):44-51.

OBJECTIVE: To examine if periodic EEG discharges (PDs) predict poor outcome and development of epilepsy in patients with acute brain illnesses irrespective of underlying cerebral pathology. METHODS: In case-control study we retrospectively analyzed outcome of 102 patients with PDs and 102 age-, gender- and etiology matched controls without PDs. RESULTS: Of cases, 46.1% had lateralized PDs (LPDs), 3.9% bilateral PDs (BIPDs), 15.7% generalized PDs (GPDs) and 34.3% had combinations thereof. Etiology: Stroke was most common cause of LPDs (53%), cardiac arrest of GPDs (10.5%), previous stroke, CNS infection, anoxia and metabolic encephalopathy all caused 1 case of BIPDs...

See full abstract 

The socioeconomic consequences of multiple sclerosis: a controlled national study. Jennum P, Wanscher B, Frederiksen J, Kjellberg J. Eur Neuropsychopharmacol. 22(1): 36-43, 2012. 

The objective of the study was to determine healthcare costs and indirect illness costs in MS patient in a national sample. We used all national records from the Danish National Patient Registry (1998-2006), and identified 10,849 MS patients which were compared with 43,396 randomly age-, sex- and social matched citizens. Patients with MS had significantly higher rates of health-related contact and medication use and very low employment rate which incurred a higher socioeconomic cost...

see full abstract

The socioeconomic consequences of optic neuritis with and without multiple sclerosis: a controlled national study. Jennum P, Frederiksen JL, Wanscher B, Kjellberg J. Acta Neurol Scand. 2013 Apr;127(4):242-50. 

OBJECTIVES: Optic neuritis (ON) often precedes multiple sclerosis (MS). MS is associated with a significant socioeconomic burden. However, the burden of ON with and without MS before and after its diagnosis has never been calculated. METHODS: Using complete national records from the Danish National Patient Registry (1998-2006), we identified 1677 patients with ON and compared them with 6708 randomly selected citizens matched for age, sex and geography. A societal perspective is taken towards the cost analyses...

see full abstract

The spatial distribution of age-related white matter changes as a function of vascular risk factors-Results from the LADIS study. Rostrup E, Gouw AA, Vrenken H, Van Straaten ECW, Ropele S, Pantoni L,Inzitari D, Barkhof F, Waldemar G & on behalf of the LADIS study group: NeuroImage 60:1597-1607, 2012. 

The aim of this study was to investigate the spatial distribution of WMH in normally functioning elderly subjects. We introduce a voxel-based approach in which lesion probability is mapped as a function of clinical risk factors using logistic regression, and validate the method using simulated datasets. The method was then applied in a total of 605 participants of the LADIS study (age 74 ± 5 years, all with WMH), and the location of manually delineated WMH was investigated after spatial normalisation. Particularly strong and widespread associations were found for age, gender and hypertension...

See full abstract

Validation of a novel automatic sleep spindle detector with high performance during sleep in middle aged subjects. Wendt SL, Christensen JA, Kempfner J, Leonthin HL, Jennum P, Sorensen HB: Conf Proc IEEE Eng Med Biol Soc. Aug 4250-3, 2012 doi: 10.1109/EMBC.2012.6346905. PubMed PMID: 23366866, 2012. 

The purpose of this study is to develop and validate a fast and reliable sleep spindle detector with high performance in middle aged subjects. An automatic sleep spindle detector using a bandpass filtering approach and a time varying threshold was developed. The validation was done on sleep epochs from EEG recordings with manually scored sleep spindles from 13 healthy subjects with a mean age of 57.9 ± 9.7 years...

See full abstract

 Program 2 - Molecular and Cellular: Muscle and MatrixTil toppen

5’- AMP Activated Protein Kinase is involved in the regulation of myocardial ß-oxidative capacity in mice. Stride N, Larsen S, Treebak JT, Hansen CN, Hey-Mogensen M, Speerschneider T, Jensen TE, Jeppesen J, Wojtaszewski JFP, Køber L, Dela F. Frontiers in Cardiac Muscle Physiology 3(33), 2012. 

5'-adenosine monophosphate-activated protein kinase (AMPK) is considered central in regulation of energy status and substrate utilization within cells. In heart failure the energetic state is compromised and substrate metabolism is altered. We hypothesized that this could be linked to changes in AMPK activity and we therefore investigated mitochondrial oxidative phosphorylation capacity from the oxidation of long- and medium-chain fatty acids (LCFA and MCFA) in cardiomyocytes from young and old mice expressing a dominant negative AMPKα2 (AMPKα2-KD) construct and their wild type (WT) littermates...

See full abstract

See full text

Adverse Metabolic Risk Profiles Independent of Aerobic Fitness and Fatness in Greenlandic Inuit Children. Munch-Andersen T, Sorensen K, Andersen LB, Aachmann-Andersen N, Aksglæde L, Juul A, Helge JH. Obesity. In press, 2012.

Aging Affects the Transcriptional Regulation of Human Skeletal Muscle Disuse Atrophy. Suetta C, Frandsen U, Jensen L, Jensen M, Jespersen JG, Hvid LG, Bayer M, Petersson SJ, Schrøder HD, Andersen JL, Heinemeier KM, Aagaard P, Schjerling P, Kjaer M: PLoS ONE 7(12): e51238, 2012. 

In the present study, muscle atrophy was induced by immobilization in healthy old and young individuals to study the time-course and transcriptional factors underlying human skeletal muscle atrophy. The results reveal that irrespectively of age, mRNA expression levels of MuRF-1 and Atrogin-1 increased in the very initial phase (2-4 days) of human disuse-muscle atrophy along with a marked reduction in PGC-1α and PGC-1β (1-4 days) and a ~10% decrease in myofiber size (4 days).

See full abstract

Angiotensin II-induced reduction in exercise capacity is associated with increased oxidative stress in skeletal muscle. Inoue N, Kinugawa S, Suga T, Yokota T, Hirabayashi K, Kuroda S, Okita K, Tsutsui H. Am J Physiol Heart Circ Physiol 302, H1202-10, 2012. 

Angiotensin II (ANG II)-induced oxidative stress has been known to be involved in the pathogenesis of cardiovascular diseases. We have reported that the oxidative stress in skeletal muscle can limit exercise capacity in mice (16). We thus hypothesized that ANG II could impair the skeletal muscle energy metabolism and limit exercise capacity via enhancing oxidative stress. ANG II (50 ng·kg(-1)·min(-1)) or vehicle was infused into male C57BL/6J mice for 7 days via subcutaneously implanted osmotic minipumps. ANG II did not alter body weight, skeletal muscle weight, blood pressure, cardiac structure, or function...

see full abstract

Biomarkers of mitochondrial content in skeletal muscle of healthy young human subjects. Larsen S, Nielsen J, Hansen CN, Nielsen LB, Wibrand F, Stride N, Schroder HD, Boushel R, Helge JW, Dela F, Hey-Mogensen M. Journal of Physiology 590(14): 3349-3360, 2012. 

The purpose of this study was to determine how closely associated these commonly used biochemical measures are to muscle mitochondrial content and OXPHOS. Sixteen young healthy male subjects were recruited for this study. Subjects completed a graded exercise test to determine maximal oxygen uptake (VO2peak) and muscle biopsies were obtained from the vastus lateralis. Mitochondrial content was determined using transmission electron microscopy imaging and OXPHOS was determined as the maximal coupled respiration in permeabilized fibres. Biomarkers of interest were citrate synthase (CS) activity, cardiolipin content, mitochondrial DNA content (mtDNA), complex I–V protein content, and complex I–IV activity...

see full abstract 

Blood flow restriction exercise in sprinters and endurance runners. Takada S, Okita K, Suga T, Omokawa M, Morita N, Horiuchi M, Kadoguchi T, Takahashi M, Hirabayashi K, Yokota T, Kinugawa S, Tsutsui H. Med Sci Sports Exerc 44: 413-419, 2012. 

We demonstrated that blood flow restriction (BFR) remarkably enhances muscular metabolic stress in resistance exercise, although there is a wide range of individual differences in the responses. It is possible that these differences could be due to training status and muscular physiological characteristics. We investigated intramuscular metabolic responses during low-intensity resistance exercise with BFR between two different types of track athletes...

See full abstract

Ceramide content is higher in type I compared to type II fibers in obesity and type 2 diabetes mellitus. Kristensen D, Prats C, Larsen S, Ara I, Dela F, Helge JW. Acta Diabetol. 2012 Feb 19.  

This study investigated fiber-type-specific muscle ceramide content in obese subjects and type 2 diabetes patients. Two substudies, one which compared type 2 diabetes patients to both lean- and obese BMI-matched subjects and the other study which compared lean body-matched post-obese, obese, and control subjects, were performed. A fasting blood sample was obtained and plasma insulin and glucose determined. A muscle biopsy was obtained from deltoideus and vastus lateralis, and fiber-type ceramide content was determined by fluorescence immunohistochemistry...

see full abstract

Changes in physical activity and the risk of myocardial infarction, ischemic heart disease, and all-cause mortality. Petersen CB, Grønbæk M, Helge JW, Thygesen LC, Tolstrup JS. Eur J Epidemiology 27 (2): 91-99, 2012. 

We examined the association between changes in leisure time physical activity and the risk of myocardial infarction (MI), ischemic heart disease (IHD), and all-cause mortality as well as changes in blood pressure in 4,487 men and 5,956 women in the Copenhagen City Heart Study. Physical activity was measured in 1976-1978 and 1981-1983 and participants were followed in nation-wide registers until 2009...

See full abstract

Clinical characteristics and outcomes of dilated phase of hypertrophic cardiomyopathy: Report from the registry data in Japan. Goto D, Kinugawa S, Hamaguchi S, Sakakibara M, Tsuchihashi-Makaya M, Yokota T, Yamada S, Yokoshiki H, Tsutsui H. J Cardiol, 2013 Jan;61(1):65-70. 

We compared the characteristics, treatments, and outcomes in patients with heart failure (HF) due to D-HCM vs. DCM by using national registry data in Japan. Patients with D-HCM (n=41) were more likely to be male, have prior stroke, atrial fibrillation, and sustained ventricular tachycardia or ventricular fibrillation compared with DCM (n=486). Echocardiography demonstrated that D-HCM patients had smaller LV end-systolic diameter, higher ejection fraction, and greater wall thickness. Treatments for HF including angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, β-blocker, and spironolactone were similar between groups except for higher use of amiodarone, warfarin, and implantable cardioverter-defibrillator for D-HCM. Mortality was significantly higher in patients with D-HCM (29.7% vs. 14.4%; p<0.05). Sudden death tended to be higher also in D-HCM (8.1% vs. 2.6%; p=0.06), which, however, did not reach statistical significance. CONCLUSIONS: HF patients with D-HCM had higher mortality risk than those with DCM. Effective management strategies are critically needed to be established for D-HCM.

see full abstract

Coronary flow reserve as a link between diastolic and systolic function and exercise capacity in heart failure. Snoer M, Monk-Hansen T, Olsen RH, Pedersen LR, Nielsen OW, Rasmussen H, Dela F, Prescott E. Eur Heart J Cardiovasc Imaging. 2012 Nov 20. 

The purpose of the study was to assess the relation of coronary flow reserve (CFR) to diastolic and systolic function in heart failure and to determine which are the limiting factors for exercise capacity.METHODS AND RESULTS: Forty-seven patients with left ventricular ejection fraction (LVEF)

See full abstract

Cryopreservation of human skeletal muscle impairs mitochondrial function. Larsen S, Wright-Paradis C, Gnaiger E, Helge JW, Boushel R: Cryo Letters 33(3): 169-175, 2012. 

The aim of the present study was to investigate if mitochondria in human skeletal muscle maintain functionality after long term cryopreservation (1 year). Skeletal muscle samples were preserved in dimethyl sulfoxide (DMSO) for later analysis. Human skeletal muscle fibres were thawed and permeabilised with saponin, and mitochondrial respiration was measured by high-resolution respirometry. The capacity of oxidative phosphorylation was significantly (P < 0.05) reduced in cryopreserved human skeletal muscle samples. Cryopreservation impaired respiration with substrates linked to Complex I more than for Complex II (P < 0.05). Addition of cytochrome c revealed an increase in respiration indicating cytochrome c loss from the mitochondria. The results from this study demonstrate that normal mitochondrial functionality is not maintained in cryopreserved human skeletal muscle samples.

see full abstract

Design and rationale for the PREVAIL study: effect of e-Health individually tailored encouragements to physical exercise on aerobic fitness among adolescents with congenital heart disease – a randomized clinical trial. Klausen SH, Mikkelsen UR, Hirth A, Wetterslev J, Kjærgaard H, Søndergaard L, Andersen LL. American Heart Journal 163(4): 549-56, 2012. 

This trial is a nationwide interactive e-Health rehabilitation study lasting 1 year, centered on interactive use of mobile phone and Internet technology. We hypothesize that e-Health encouragements and interactive monitoring of intensive exercise for 1 year can improve physical fitness, physical activity, and health-related quality of life. Two hundred sixteen adolescents (age, 13-16 years) with surgically corrected complex CHD but without significant hemodynamic residual defects and no restrictions to participate in physical activity are in the process of being enrolled by invitation after informed consent. Physical fitness is measured as the maximal oxygen uptake (Vo(2)) at baseline and after 12 months by an assessor blinded to the randomization group...

see full abstract

Daily physical activity alleviates the adverse effects of western diet among Inuit in Northwest Greenland. Munch-Andersen T, Olsen DB, Søndergaard H, Daugaard J, Bysted A, Christensen DL, Saltin B, Helge JW. Int. J. Circum Polar Health 19: 71;17342-, 2012.

Decreased mitochondrial oxidative phosphorylation capacity in the human heart with left ventricular systolic dysfunction. Stride N, Larsen S, Hey-Mogensen M, Sander K, Lund JT, Gustafsson F, Køber L, Dela F. European Journal of Heart Failure. Eur J Heart Fail. 2013 Feb;15(2):150-7.

The study aim was to test mitochondrial OXPHOS capacity in LVSD myocardium compared with OXPHOS capacity in a comparable patient group without LVSD. METHODS AND RESULTS: Myocardial biopsies were obtained from the left ventricle during cardiac valve or left ventricular assist device (LVAD) surgery. Patients were stratified according to left ventricular ejection fraction (LVEF) into LVSD (LVEF <45%, n = 14) or CONTROL (LVEF >45%, n = 15). Mitochondrial respiration was measured in muscle fibres with addition of non-fatty acid substrates or octanoyl-l-carnitine, a medium chain fatty acid (MCFA).

See full abstract

Differentially activated macrophages orchestrate myogenic precursor cell fate during human skeletal muscle regeneration. Saclier M, Yacoub-Yossef H, Mackey AL, Arnold L, Ardjoune H, Magnan M, Sailhan F, Chelly J, Pavlath GK, Mounier R, Kjaer M, Chazaud B. Stem Cells. Stem Cells. 2013 Feb;31(2):384-96. 

Macrophages (MPs) exert either beneficial or deleterious effects on tissue repair, depending on their activation/polarization state. They are crucial for adult skeletal muscle repair, notably by acting on myogenic precursor cells. However, these interactions have not been fully characterized. Here, we explored both in vitro and in vivo, in human, the interactions of differentially activated MPs with myogenic precursor cells (MPCs) during adult myogenesis and skeletal muscle regeneration...

See full abstract

Effects of 2 weeks lower limb immobilization and two separate rehabilitation regimens on gastrocnemius muscle protein turnover signalling and normalization genes. Nedergaard A, Jespersen JG, Pingel J, Christensen B, Sroczynski N, Langberg H, Kjaer M, Schjerling P. BMC Research Notes 28: 166-172, 2012. 

To investigate the phosphorylation and expression of candidate key molecular muscle mass regulators after immobilization and subsequent rehabilitation we performed two separate studies. METHODS: We immobilized the lower limb for 2 weeks followed by the in-house hospital standard physiotherapy rehabilitation (Study 1). Secondly, we conducted an intervention study using the same 2 weeks immobilization protocol during which protein/carbohydrate supplementation was given. This was followed by 6 weeks of rehabilitation in the form of resistance training and continued protein/carbohydrate supplementation (Study 2)...

see full abstract

see full text

Effects of anti-tumor necrosis factor therapy on body composition and insulin sensitivity in patients with psoriasis. Kofoed K, Clemmensen A, Mikkelsen UR, Simonsen L, Andersen O, Gniadecki R. Archives of Dermatology 148(9): 1089-91, 2012. 

Epidemiologic studies have shown an association between psoriasis and cardiovascular diseases. An interesting but unproven hypothesis ascribes this association to the psoriatic march, the process by which inflammatory mediators released in the course of the psoriatic autoimmune reaction cause insulin resistance, which ultimately leads to atherosclerosis. Tumor necrosis factor (TNF) is a proinflammatory cytokine that impairs response to insulin in adipocytes and muscle cells via inhibition of tyrosine kinase activity of the insulin receptor, activation of peroxisome proliferator–activated receptor-δ, and changes in secretion of adipokines. For the present study, we investigated the effect of anti-TNF treatment on insulin resistance and body composition in patients with psoriasis.

See full abstract

Effects of estrogen replacement and lower androgen status on skeletal muscle collagen and myofibrillar protein synthesis in postmenopausal women. Hansen M, Skovgaard D, Reitelseder S, Holm L, Langberg H, Kjaer M: J Gerontology A Biological and Medical Sciences 67(10): 1005-13, 2012. 

Our aim was to determine synthesis rate of myofibrillar and collagen proteins in 20 postmenopausal women, who were either nonusers (Controls) or users of estrogen replacement therapy (ERT) after hysterectomy/oophorectomy. Myofibrillar and muscle collagen protein fractional synthesis rate (FSR) were determined in a nonexercised leg and 24 hours after exercise in the contralateral leg. A significant interaction between treatment and mechanical loading was observed in myofibrillar protein FSR...

see full abstract

Effect of multiple set on intramuscular metabolic stress during low-intensity resistance exercise with blood flow restriction. Suga T, Okita K, Takada S, Omokawa M, Kadoguchi T, Yokota T, Hirabayashi K, Takahashi M, Morita N, Horiuchi M, Kinugawa S, Tsutsui H. Eur J Appl Physiol. 112, 3915-20, 2012. 

Our previous study reported that intramuscular metabolic stress during low-intensity resistance exercise was significantly enhanced by combining blood flow restriction (BFR); however, they did not reach the levels achieved during high-intensity resistance exercise. That study was performed using a single set of exercise; however, usual resistance exercise consists of multiple sets with rest intervals. Therefore, we investigated the intramuscular metabolic stress during multiple-set BFR exercises, and compared the results with those during multiple-set high-intensity resistance exercise.

See full abstract

See full text

Effects of transdermal estrogen on collagen turnover at rest and in response to exercise in postmenopausal women.Pingel J, Langberg H, Skovgård D, Koskinen S, Flyvbjerg A, Frystyk J, Kjær M, Hansen M. Journal of Applied Physiology 113: 1040-1047, 2012. 

Menopause is associated with loss of collagen content in the skin and tendon as well as accumulation of noncontractile tissue in skeletal muscle. The relative role of hormones and physical activity on these changes is not known. Accordingly, in a randomized, controlled, crossover study we investigated effects of transdermal estrogen replacement therapy (ERT) on type I collagen synthesis in tendon and skeletal muscle in 11 postmenopausal women...

See full abstract

Effect of an internet-based intervention to increase physical activity among physically inactive persons in a real-life setting. Hansen AV, Grønbæk M, Helge JW, Severin M, Curtis T, Tolstrup JS: J Med Internet Res. 14(5): E145 1-14, 2012. 

OBJECTIVE: To examine whether access to a website with individually tailored feedback and suggestions on how to increase PA led to improved PA, anthropometrics, and health measurements. METHODS: Physically inactive adults were randomly assigned to either an intervention (website) (n = 6055) or a no-intervention control group (n = 6232) in 2008. The intervention website was founded on the theories of stages of change and of planned behavior and, apart from a forum page where a physiotherapist answered questions about PA and training, was fully automated. RESULTS: Less than 22.0% (694/3156) of the participants logged on to the website once and only 7.0% (222/3159) logged on frequently. We found no difference in PA level between the website and control groups at 3- and 6-month follow-ups. CONCLUSION: Based on our findings, we suggest that active users of a Web-based PA intervention can improve their level of PA. However, for unmotivated users, single-tailored feedback may be too brief.

See full text

Expression of extracellular matrix components and related growth factors in human tendon and muscle after acute exercise. Heinemeier KM, Bjerrum SS, Schjerling P, Kjaer M: Scand J Med Sci Sports. 2011 Nov 23. 

Young men performed 1 h of one-leg kicking at 67% of max workload. Biopsies were taken from the patellar tendon and vastus lateralis muscle of each leg at 2 (n = 10), 6 (n = 11), or 26 h (n = 10) after exercise. Levels of messenger ribonucleic acid mRNA for collagens, noncollagenous matrix proteins, and growth factors were measured with real-time reverse transcription polymerase chain reaction. In tendon, gene expression was unchanged except for a decrease in insulin-like growth...

see full abstract

Erythropoietin treatment enhances muscle mitochondrial capacity in humans. Plenge U, Belhage B, Guadalupe-Grau A, Andersen PR, Lundby C, Dela F, Stride N, Pott FC, Helge JW, Boushel R. Frontiers in Physiology 3: 50, 2012. 

Erythropoietin (Epo) treatment has been shown to induce mitochondrial biogenesis in cardiac muscle along with enhanced mitochondrial capacity in mice. We hypothesized that recombinant human Epo (rhEpo) treatment enhances skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity in humans. In six healthy volunteers rhEpo was administered by sub-cutaneous injection over 8 weeks with oral iron (100 mg) supplementation taken daily.

see full abstract

see full text

Fear of falling and changed functional ability following hip fracture among community-dwelling elderly people: an explanatory sequential mixed method study. Jellesmark A, Herling SF, Egerod I, Beyer N. Disability & Rehabilitation 34: 2124-31, 2012. 

The aims of the study were to assess self-reported fear of falling (FOF) and functional ability among community-dwelling elderly people 3-6 months post hospital discharge after a hip fracture, to investigate the association between FOF and functional ability, and to explore the lived experience of FOF and disability when recovering from a hip fracture...

see full abstract

Four days of muscle disuse impairs single fiber contractile function in young and old healthy men. Hvid LG, Suetta C, Aagaard P, Kjaer M, Frandsen U, Ortenblad N: Exp Gerontol. 2013 Feb;48(2):154-61. 

The purpose of the study was to investigate the effects of 4 days of disuse (knee brace) on contractile function of isolated vastus lateralis fibers (n=486) from 11 young (24.3±0.9 yrs) and 11 old (67.2±1.0 yrs) healthy men having comparable levels of physical activity...

see full abstract

Gene expression in distinct regions of rat tendons in response to jump training combined with anabolic androgenic steroid administration. Marqueti RC, Heinemeier KM, Durigan JL, de Andrade Perez SE, Schjerling P, Kjaer M. European Journal of Applied Physiology 112: 1505-15, 2012. 

The aim of this study was to evaluate the expression of key genes responsible for tendon remodeling of the proximal and distal regions of calcaneal tendon (CT), intermediate and distal region of superficial flexor tendon (SFT) and proximal, intermediate and distal region of deep flexor tendon (DFT) submitted to 7 weeks of jumping water load exercise in combination with AAS administration. Wistar male rats were grouped as follows: sedentary (S), trained (jumping water load exercise) (T), sedentary animals treated with AAS (5 mg/kg, twice a week) and animals treated with AAS and trained (AAST). mRNA levels of COL1A1, COL3A1, TIMP-1, TIMP-2, MMP-2, IGF-IEa, GAPDH, CTGF and TGF-β-1 were evaluated by quantitative PCR...

see full abstract

GH/IGF-I axis and matrix adaptation of the musculotendinous tissue to exercise in humans. Heinemeier KM, Mackey AL, Doessing S, Hansen M, Bayer ML, Nielsen RH, Herchenhan A, Malmgaard-Clausen, NM, Kjaer M: Scandinavian Journal of Medicine & Science in Sports 22: e1-7, 2012. 

Exercise is not only associated with adaptive responses within skeletal muscle fibers but also with induction of collagen synthesis both in muscle and adjacent connective tissue. Additionally, exercise and training leads to activation of the systemic growth hormone/insulin-like growth factor I axis (GH/IGF-I), as well as increased local IGF-I expression. Although advanced age is associated with both a reduction in the GH/IGF-I axis activity, and in skeletal muscle mass (sarcopenia) as well as in tendon connective tissue, there is no direct proof linking age-related changes in the musculotendinous tissue to an impaired GH/IGF-I axis.

see full abstract

Immobilisation increases interleukin-6, but not tumor necrosis factor-a release from the leg during exercise in humans. Reihmane D, Hansen AV, Jensen MG, Kuhlman AB, Nørregaard J, Pedersen HP, Lund MT, Helge JW, Dela F. Exp Physiol. 2013 Mar;98(3):778-83. 

Data on interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) release during acute exercise are not conclusive, and information is lacking about the impact of physical inactivity. Some studies have shown an increase, but others report no changes in IL-6 and TNF-α release during exercise. We have now studied the temporal relationship of leg IL-6 and TNF-α release before and during isolated two-legged exercise after 14 days of one-leg immobilization (IM) while the other leg served as the control (CON) leg. Fifteen healthy male subjects (mean ± SEM age, 23 ± 1 years; body mass index, 23.6 ± 0.7 kg m(-2); and maximal oxygen uptake, 46.8 ± 1.4 ml kg(-1) min(-1)) performed 45 min of two-legged dynamic knee-extensor exercise at 19.6 ± 0.8 W...

See full abstract

Increase in IL-6, TNF-alpha, and MMP-9, but not sICAM-1, concentrations depends on exercise duration. Reihmane D, Jurka A, Tretjakovs P, Dela F. European Journal of Applied Physiology. Eur J Appl Physiol. 2013 Apr;113 (4):851-8. 

It has been suggested that exercise intensity is of importance in the regulation of increase in pro-inflammatory molecules, but there is still a debate about the effect of duration on these molecules. Therefore, the effect of exercise duration on the serum concentrations of interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), soluble form of intercellular adhesion molecule-1 (sICAM-1), and matrix metalloproteinase-9 (MMP-9) was studied in 22 half-marathon (HM) and 18 marathon (M) male amateur runners who completed their exercise task in 1.8 ± 0.2 (mean ± standard deviation) and 3.6 ± 0.4 h, respectively (thus, average speed was 11.7 ± 1.5 and 11.9 ± 1.8 km h(-1), respectively)...

See full abstract

Insulin and Fiber Type in Offspring of T2DM with Resistance Training and Detraining. Schofield KL, Rehrer NJ, Perry TL, Ross A, Andersen JL, Osborne H: Medicine & Science in Sports & Exercise 44: 2331-9, 2012. 

PURPOSE: Effects of resistance training and detraining on glucose and insulin responses to an oral glucose load, muscle fiber type, and muscular performance in the offspring of those with type 2 diabetes (familial insulin resistant (FIR)) were investigated. METHODS: Six FIR participants and 10 controls (C) completed 9 wk of resistance training and 9 wk of detraining. Measures of strength and power, an oral glucose tolerance test, and a muscle biopsy to determine myosin heavy chain (MHC) fiber composition were taken at baseline (T1), after training (T2), and after detraining (T3)...

See full abstract

Insulin resistance and exercise tolerance in heart failure patients: linkage to coronary flow reserve and peripheral vascular function. Snoer M, Monk-Hansen T, Olsen RH, Pedersen LR, Simonsen L, Rasmusen H, Dela F, Prescott E. Cardiovasc Diabetol 13;11(1):97, 2012. 

The aim of this study was to assess the potential role of coronary flow reserve (CFR), endothelial function and arterial stiffness in explaining this linkage. METHODS: 39 patients with LVEF < 35% (median LV ejection fraction (LVEF) 31 (interquartile range (IQ) 26-34), 23/39 of ischemic origin) underwent echocardiography with measurement of CFR. Peak coronary flow velocity (CFV) was measured in the LAD and coronary flow reserve was calculated as the ratio between CFV at rest and during a 2 minutes adenosine infusion.

See full abstract

Insulin resistance and mitochondrial function in skeletal muscle. Dela F, Helge JW. The International Journal of Biochemistry & Cell Biology 45: 11-15, 2012. 

The mechanism(s) behind the decreased ability of insulin to facilitate glucose uptake in insulin sensitive tissues as seen in type 2 diabetes is not resolved. With the rapidly increasing prevalence of this disease world-wide, and the many complications that follow the disease, large resources are used in the attempt to resolve the mechanisms of insulin resistance. In this context, a dysfunction of mitochondria in the skeletal muscle has been suggested to play a pivotal role...

See full abstract

In vitro tendon tissue development from human fibroblasts demonstrates collagen fibril diameter growth associated with a rise in mechanical strength. Herchenhan A, Bayer ML, Svensson RB, Magnusson SP, Kjaer M: Dev Dyn. 2013 Jan;242(1):2-8. doi. 

In the present study, we investigated mechanical strength, fibril size, and structure during development of tendon-like tissue from adult human tenocytes (termed tendon constructs) in vitro over 5 weeks in 3D tissue culture. The constructs displayed large elongated tendon cells aligned along the tendon axis together with collagen fibrils that increased in diameter by 50% from day 14 to 35, which approaches that observed in adult human tendon in vivo...

see full abstract

LKB1 regulates lipid oxidation during exercise independently of AMPK. Jeppesen J, Maarbjerg S, Jordy A, Sylow L, Fritzen A, Pehmøller C, Serup A, Jessen N, Thorsen K, Prats C, Qvortrup K, Dyck J, Hunter R, Sakamoto K, Thomson D, Schjerling P, Wojtaszewski J, Richter E, Kiens B: Diabetes. 2013 Jan 24. 

Here, we show that LKB1 muscle-specific knockout (LKB1 MKO) mice display decreased fatty acid (FA) oxidation during treadmill exercise. LKB1 MKO mice also show decreased muscle SIK3 activity, increased histone deacetylase 4 expression, decreased NAD(+) concentration and SIRT1 activity, and decreased expression of genes involved in FA oxidation. In AMPKα2 KO mice, substrate use was similar to that in WT mice, which excluded that decreased FA oxidation in LKB1 MKO mice was due to decreased AMPKα2 activity. Additionally, LKB1 MKO muscle demonstrated decreased FA oxidation in vitro...

see full abstract

Local administration of growth hormone stimulates tendon collagen synthesis in elderly men.Vestergaard P, Jørgensen JOL, Olesen JL, Bosnjak E, Holm L, Flystyk J, Langberg H, Kjaer M, Hansen M. Journal of Applied Physiology 113(9): 1432-38, 2012. 

Tendon collagen content and circulating growth hormone (GH) are reduced in elderly. In a placebo-controlled, double-blinded study, we examined if local injections of rhGH enhance collagen synthesis in healthy elderly men (61 ± 1 yr). Two injections of rhGH or saline (control) were injected into each of the patient's patellar tendons, respectively. Subsequently, tendon collagen fractional synthesis rate (FSR) and an indirect marker of type I collagen synthesis (PINP) were measured...

See full abstract

Local administration of insulin-like growth factor-I (IGF-I) stimulates tendon collagen synthesis in humans. Hansen M, Boesen A, Holm L, Flyvbjerg A, Langberg H, Kjaer M. Scand J Med Sci Sports. Scand J Med Sci Sports, 2012 Jan 31.

The purpose of this study was to study whether local injections of IGF-I would have a stimulating effect on tendon collagen synthesis. Twelve healthy nonsmoking men [age 62 ± 1 years (mean ± SEM), BMI 27 ± 1] participated. Two injections of either human recombinant IGF-I (0.1 mL Increlex©) or saline (control) into each patellar tendon were performed 24-h apart, respectively. Tendon collagen fractional synthesis rate (FSR) was measured by stable isotope technique in the hours after the second injection...

see full abstract

Local biochemical and morphological differences in human Achilles tendinopathy: a case control study. Pingel J, Fredberg U, Qvortrup K, Larsen JO, Schjerling P, Heinemeier KM, Kjaer M, Langberg H: BMC Musculoskeletal Disorders 13: 53-59, 2012. 

The aim of the present study was to describe biochemical and morphological differences in chronic Achilles tendinopathy. The expressions of growth factors, inflammatory mediators and tendon morphology were determined in both chronically diseased and healthy tendon parts. METHODS: Thirty Achilles tendinopathy patients were randomized to an expression-study (n = 16) or a structural-study (n = 14). Biopsies from two areas in the Achilles tendon were taken and structural parameters: fibril density, fibril size, volume fraction of cells and the nucleus/cytoplasm ratio of cells were determined...

See full abstract

Low-intensity exercise can increase muscle mass and strength proportionally to enhanced metabolic stress under ischemic conditions. Takada S, Okita K, Suga T, Omokawa M, Kadoguchi T, Sato T, Takahashi M, Yokota T, Hirabayashi K, Morita N, Horiuchi M, Kinugawa S, Tsutsui H. J Appl Physiol 113: 199-205, 2012. 

Skeletal muscle bulk and strength are becoming important therapeutic targets in medicine. To increase muscle mass, however, intensive, long-term mechanical stress must be applied to the muscles, and such stress is often accompanied by orthopedic and cardiovascular problems. We examined the effects of circulatory occlusion in resistance training combined with a very low-intensity mechanical load on enhancing muscular metabolic stress and thereby increasing muscle bulk...

See full abstract

Mechanical properties of human patellar whole tendon at the hierarchical levels of tendon and fibril. Svensson RB, Hansen P, Hassenkam T, Haraldsson BT, Aagaard P, Kovanen V, Krogsgaard M, Kjaer M, Magnusson SP: Journal of Applied Physiology 112(3): 419-26, 2012. 

Tendons are strong hierarchical structures, but how tensile forces are transmitted between different levels remains incompletely understood. Collagen fibrils are thought to be primary determinants of whole tendon properties, and therefore we hypothesized that the whole human patellar tendon and its distinct collagen fibrils would display similar mechanical properties. Human patellar tendons (n = 5) were mechanically tested in vivo by ultrasonography. Biopsies were obtained from each tendon, and individual collagen fibrils were dissected and tested mechanically by atomic force microscopy...

See full abstract

Metformin treated patients with type 2 diabetes have normal mitochondrial complex I respiration. Larsen S, Rabøl R, Hansen CN, Madsbad S, Helge JW, Dela F. Diabetologia 55: 443-449, 2012. 

AIMS and HYPOTHESIS: The glucose-lowering drug metformin has been shown to inhibit complex I of the mitochondrial electron transport chain in skeletal muscle. To investigate this effect in vivo we studied skeletal muscle mitochondrial respiratory capacity and content from patients with type 2 diabetes treated with metformin (n = 14) or sulfonylurea (n = 8) and healthy control (n = 18) participants. METHODS: Mitochondrial respiratory capacity was measured ex vivo in permeabilised muscle fibres obtained from the vastus lateralis muscle of all participants. The respiratory response to in vitro titration with metformin was measured in controls. Citrate synthase (CS) activity, and fasting plasma glucose, insulin and HbA(1c) levels were measured and body composition was determined...

see full abstract

Moderate loading of the human osteoarthritic knee joint leads to lowering of intraarticular cartilage oligometric matrix protein. Helmark IC, Petersen MC, Christensen HE, Kjaer M, Langberg H: Rheumatology International 32: 1009-1015, 2012. 

The purpose of the present study was to investigate the direct effects of a load-bearing exercise upon cartilage in a single, human osteoarthritic joint determined by biochemical markers of cartilage turnover and inflammation in the synovial fluid (SF), serum and urine. Eleven subjects with OA of the knee(s), but with no other joint- or inflammatory disorders, volunteered for the study and had samples of blood, urine and synovial fluid drawn both at baseline and following 30-min one-legged knee-extension exercise...

see full abstract

Muscle ceramide content is similar after 3 weeks consumption of fat or carbohydrate diet in a crossover design in patients with type 2 diabetes. Helge JW, Tobin L, Drachmann T, Hellgren L, Dela F, Galbo H. European Journal of Applied Physiology 112(3): 911-918, 2012. 

This study aimed at investigating the effect of prolonged adaptation to fat- or carbohydrate-rich diet on muscle ceramide in type 2 diabetes patients, using a longitudinal crossover study. Eleven type 2 diabetes patients consumed isocaloric fat- or carbohydrate-rich diet for 3 weeks in random order. After each dietary intervention period, muscle glycogen, triacylglycerol and ceramide content and plasma concentrations of insulin, adiponectin, glucose and FFA were determined...

see full abstract

Muscle inflammatory signaling in response to 9 days of physical inactivity in young men with low compared to normal birth weight. Friedrichsen M, Ribel-Madsen R, Mortensen B, Hansen CN, Alibegovic AC, Højbjerre L, Sonne MP, Wojtaszewski JFP, Stallknecht B, Dela F, Vaag A. European Journal of Endocrinology 167(6): 829-38, 2012. 

We employed a human bed rest study including 20 young males with normal birth weight (NBW) and 20 with low birth weight (LBW) and increased risk of diabetes. METHODOLOGY: The subjects were studied before and after 9 days of bed rest using the euglycemic-hyperinsulinemic clamp and muscle biopsy excision. Muscle inflammatory status was assessed as nuclear factor-κB (NF-κB) activity and mRNA expression of the pro-inflammatory MCP1 (CCL2) and IL6 and the macrophage marker CD68. Furthermore, mRNA expression of genes central to oxidative phosphorylation (OXPHOS) was measured including ATP5O, COX7A1, NDUFB6, and UQCRB. CONCLUSIONS: Although LBW subjects exhibit disproportionately elevated CD68 mRNA expression suggesting macrophage infiltration and reduced OXPHOS gene expression when exposed to bed rest, our data altogether do not support the notion that bed rest-induced (9 days) insulin resistance is caused by increased muscle inflammation...

see full abstract

No donor age effect of human serum on collagen synthesis signaling and cell proliferation of human tendon fibroblasts. Bayer ML, Schjerling P, Heinemeier KM, Kjaer M. Mechanics of Ageing and Development 133: 246-254, 2012. 

The aim of this study was to investigate whether human serum from elderly donors would have an inhibiting effect on the expression of collagen and collagen-related genes as well as on cell proliferative capacity in tendon cells from young individuals. There was no difference in systemic TGF-β1 levels in serum obtained from young and elderly donors, and we found no difference in collagen expression when cells were subjected to human serum from elderly versus young donors. In addition, tendon cell proliferation was similar when culture medium was supplemented with serum of different donor age. These findings suggest that factors such as the cell intrinsic capacity or the tissue-specific environment rather than systemic circulating factors are important for functional capacity throughout life in human tendon cells...

See full abstract

Rehabilitation of muscle after injury – the role of anti-inflammatory drugs. Mackey AL, Mikkelsen UR, Magnusson SP, Kjaer M: Scandinavian Journal of Medicine & Science in Sports 22: e8-14, 2012. 

This review aims to provide an overview of studies investigating their effects on skeletal muscle, in particular the repair processes in injured muscle. Muscle injury occurs in diverse situations and the nature of muscle injuries varies significantly, complicating extrapolations between experimental models and "real life." Classical muscle strain injuries occur at the interphase between the muscle fibers and connective tissue, most often in the myotendinuous junction, whereas contusion or overload injury can damage both myofibers and intramuscular connective tissue. The role of NSAIDs in muscle repair is complicated by differences in injury models used, variables evaluated, and time point(s) selected for evaluations...

see full abstract

Simvastatin effects on skeletal muscle: Relation to decreased mitochondrial function and glucose Intolerance. Larsen S, Stride N, Hey-Mogensen M, Hansen CN, Bang LE, Bundgaard H, Nielsen LB, Helge JW, Dela F. Journal of American College of Cardiology. In press, 2012. 

OBJECTIVES: Glucose tolerance and skeletal muscle coenzyme Q(10) (Q(10)) content, mitochondrial density, and mitochondrial oxidative phosphorylation (OXPHOS) capacity were measured in simvastatin-treated patients (n = 10) and in well-matched control subjects (n = 9). METHODS: Plasma glucose and insulin concentrations were measured during an oral glucose tolerance test. Mitochondrial OXPHOS capacity was measured in permeabilized muscle fibers by high-resolution respirometry in a cross-sectional design. Mitochondrial content (estimated by citrate synthase [CS] activity, cardiolipin content, and voltage-dependent anion channel [VDAC] content) as well as Q(10) content was determined...

see full abstract

Skeletal muscle mitochondrial respiration in AMPKa2 kinase dead mice. Larsen S, Møller Kristensen J, Stride N, Wojtaszewski JFP, Helge JW, Dela F. Acta Physiologica 205(2): 314-320, 2012. 

AIM: To study whether the phenotypical characteristics (exercise intolerance; reduced spontaneous activity) of the AMPKα2 kinase-dead (KD) mice can be explained by a reduced mitochondrial respiratory flux rates (JO(2) ) in skeletal muscle. Secondly, the effect of the maturation process on JO(2) was studied. METHODS: In tibialis anterior (almost exclusively type 2 fibres) muscle from young (12-17 weeks, n = 7) and mature (25-27 weeks, n = 12) KD and wild-type (WT) (12-17 weeks, n = 9; 25-27 weeks, n = 11) littermates, JO(2) was quantified in permeabilized fibres ex vivo by respirometry, using a substrate-uncoupler-inhibitor-titration (SUIT) protocol: malate, octanoyl carnitine, ADP and glutamate (GMO(3) ), + succinate (GMOS(3) ), + uncoupler (U) and inhibitor (rotenone) of complex I respiration. Citrate synthase (CS) activity was measured as an index of mitochondrial content...

see full abstract

Sleepdisordered breathing is an independent risk factor of aborted sudden cardiac arrest in patients with coronary artery spasm. Sakakibara M, Yamada S, Kamiya K, Yokota T, Oba K, Tsutsui H: Circ J. 76: 2204-10, 2012. 

This study evaluated the breathing patterns during sleep in CS patients with a prior history of aborted SCA. METHODS AND RESULTS: This study enrolled 24 patients (age 61.6 ± 11.0 years, male/female 19/5) with CS proven by an acetylcholine provocation test. They were divided into 2 groups: prior history of aborted SCA due to fatal arrhythmia (SCA group; n=9) and no such history (no-SCA group; n=15). Patients underwent overnight polysomnography with ambulatory electrocardiography...

See full abstract

The anabolic potential of dietary protein intake on skeletal muscle is prolonged by prior light-load exercise. Bechshoeft R, Dideriksen KJ, Reitelseder S, Scheike T, Kjaer M, Holm L. The anabolic potential of dietary protein intake on skeletal muscle is prolonged by prior light-load exercise. Clin Nut 2013 Apr;32(2):236-44r. (Accepted, 2012) 

BACKGROUND & AIMS: Hyperaminoacidemia stimulates myofibrillar fractional synthesis rate (myoFSR) transiently in resting skeletal muscle. We investigated whether light-load resistance exercise can extent this responsiveness. METHODS: Ten healthy males exercised one leg with a light-load resistance-like exercise at 16% of 1 repetition maximum and received oral protein boluses every hour for a 10-h period. Their myoFSR was determined by [1-C]-leucine incorporation. Muscle biopsies were obtained from the resting (REST) and exercised (EXC) muscles every 2.5-h in the protein-fed period...

See full abstract

The effect of acute exercise on collagen turnover in human tendons: influence of prior immobilization period. Moerch L, Pingel J, Boesen M, Kjaer M, Langberg H. Eur J Appl Physiol. 2013 Feb;113(2):449-55. 

We tested the effect of prolonged load deprivation on the acute loading-induced collagen turnover in human tendons, by applying the same absolute load to a relative untrained Achilles tendon (2-week immobilization period prior to acute loading) and a habitually loaded contra-lateral Achilles tendon, respectively, within the same individuals. Eight untrained, healthy males had one lower limb totally immobilized for 2 weeks, whereas the contra-lateral leg was used habitually...

see full abstract

The effects of immobilization on patellar tendon mechanical properties in old men. Couppe C, Suetta C, Kongsgaard M, Hansen P, Hviid L, Dahl M, Bojsen-Moller J, Aagaard P, Kjaer M, Magnusson SP. Clinical Biomechanics 27(9): 949-54, 2012. 

The purpose was to examine the effects of short-term unilateral immobilization on the structural and mechanical properties of the patellar tendon in older men and younger men, in vivo. Eight older men and eight younger men underwent 14 days of unilateral immobilization. All individuals were assessed on both sides before and after the intervention. MRI was used to assess whole patellar tendon dimensions. The mechanical properties of the patellar tendon were assessed using simultaneous force and ultrasonographic measurements during isometric ramp contractions...

See full abstract

The influence of age and aerobic fitness: Effects on mitochondrial respiration in skeletal muscle. Larsen S, Hey-Mogensen M, Rabøl R, Stride N, Helge JW, Dela F. Acta Physiologica 205(3): 423-432, 2012. 

AIM: Mitochondrial function has previously been studied in ageing, but never in humans matched for maximal oxygen uptake ((V)·O2max). Furthermore, the influence of ageing on mitochondrial substrate sensitivity is not known. METHODS: Skeletal muscle mitochondrial respiratory capacity and mitochondrial substrate sensitivity were measured by respirometry in young (23 ± 3 years) and middle-aged (53 ± 3 years) male subjects with similar (V)·O2max. Protocols for respirometry included titration of substrates for complex I (glutamate), complex II (succinate) and both (octanoyl carnitine) for calculation of substrate sensitivity (C(50) ). Myosin heavy chain (MHC) isoforms, citrate synthase (CS) and β-hydroxy-acyl-CoA-dehydrogenase (HAD) activity, mitochondrial DNA (mtDNA) content, protein levels of complexes I-V and antioxidant defence system [manganese superoxide dismutase (MnSOD)] were measured...

see full abstract

Two Weeks of Metformin treatment Enhances Mitochondrial Respiration in Skeletal Muscle of AMPK Kinase Dead But Not Wild Type Mice. Kristensen JM, Larsen S, Helge JW, Dela F, Wojtaszewski J. PLoS One. 2013;8(1):e53533. doi: 10.1371/journal.pone.0053533. Epub 2013 Jan 14. 

We hypothesized that potential effects of in vivo metformin treatment on mitochondrial function and protein expressions in skeletal muscle are dependent upon AMPK signaling. We investigated this by two weeks of oral metformin treatment of muscle specific kinase dead α(2) (KD) AMPK mice and wild type (WT) littermates. We measured mitochondrial respiration and protein activity and expressions of key enzymes involved in mitochondrial carbohydrate and fat metabolism and oxidative phosphorylation. Mitochondrial respiration, HAD and CS activity, PDH and complex I-V and cytochrome c protein expression were all reduced in AMPK KD compared to WT tibialis anterior muscles. Surprisingly, metformin treatment only enhanced respiration in AMPK KD mice and thereby rescued the respiration defect compared to the WT mice...

see full abstract

see full text

Uphill running improves rat Achilles tendon tissue mechanical properties and alters gene expression without inducing pathological changes. Heinemeier KM, Skovgaard D, Bayer ML, Qvortrup K, Kjaer A, Kjaer M, Magnusson SP, Kongsgaard M. Journal of Applied Physiology 113: 827-836, 2012. 

Our aim was to test a previously proposed rat model for Achilles tendon overuse. Ten adult male Sprague-Dawley rats ran on a treadmill with 10° incline, 1 h/day, 5 days/wk (17-20 m/min) for 12 wk and were compared with 12 control rats. Histological, mechanical, and gene-expression changes were measured on the Achilles tendons after the intervention, and local tendon glucose-uptake was measured before and after the intervention with positron emission tomography. No differences were detected between runners and controls in tissue histology or in glucose uptake, indicating that tendon pathology was not induced...

see full abstract

Validation of an Internet-based long version of the International Physical Activity Questionnaire in Danish adults using combined accelerometry and heart rate monitoring. Hansen AV, Dahl Petersen I, Helge JW, Grønbæk M, Tolstrup JS. J Phys Act Health. 2013 Feb 8. 

BACKGROUND: The International Physical Activity Questionnaire (IPAQ) is commonly used in surveys but reliability and validity has not been established in the Danish population. METHODS: Among participants in the Danish Health Examination survey 2007-2008, 142 healthy participants (45% men) wore a unit that combined accelerometry and heart rate monitoring (Acc+HR) for 7 consecutive days and then completed the IPAQ. Background data were obtained from the survey. RESULTS: PAEE from the two methods was significantly positively correlated (0.28 and 0.49 for women and men, respectively). Men significantly overestimated PAEE by IPAQ (56.2 vs. 45.3 kJ/kg/day, IPAQ: Acc+HR, P<0.01), while the difference was non-significant for women (40.8 vs. 44.4 kJ/kg/day). CONCLUSIONS: This Danish Internet-based version of the long IPAQ had modest validity and reliability when assessing PAEE at population level...

see full abstract

 Program 3 - Body and LifeTil toppen

A Comparison of three Methods to Measure Asthma in Epidemiologic Studies: Results from the Danish National Birth Cohort. Hansen S, Strøm M, Maslova E, Mortensen EL, Granström C, Olsen SF. PLoS ONE. 7(5): e36328. Doi:10.1371/journal.pone.0036328, 2012. 

We compared three methods of measuring asthma in the Danish National Birth Cohort (n>50.000). When the children were 7 years old, the prevalence of asthma was estimated from a self-administered questionnaire using parental report of doctor diagnoses, ICD-10 diagnoses from a population-based hospitalization registry, and data on anti-asthmatic medication from a population-based prescription registry. Highest prevalence of asthma was found using the prescription registry (32.2%) followed by the self-report (12.0%) and the hospitalization registry (6.6%). We found a substantial non-overlap between the methods (kappa = 0.21-0.38). When all three methods were combined the asthma prevalence was 3.6%. In conclusion, self-reported asthma, ICD-10 diagnoses from a hospitalization registry and data on anti-asthmatic medication use from a prescription registry lead to different prevalences of asthma in the same cohort of children. The non-overlap between the methods may be due to different abilities of the methods to identify cases with different phenotypes, in which case they should be treated as separate outcomes in future aetiological studies.

see full text

A one-item workability measure mediates work demands, individual resources and health in the prediction of sickness absence. Thorsen SV, Burr H, Diderichsen F, Bjorner JB: Int Arch Occup Environ Health. 2012 Aug 28. 

OBJECTIVES: The study tested the hypothesis that a one-item workability measure represented an assessment of the fit between resources (the individuals' physical and mental health and functioning) and workplace demands and that this resource/demand fit was a mediator in the prediction of sickness absence. We also estimated the relative importance of health and work environment for workability and sickness absence...

See full abstract

Activity participation and cognitive ageing in the Glostrup 1914 cohort from age 50 to 85. Gow AJ, Mortensen EL, Avlund K. J Am Geriatr Soc. 60: 1831-1838, 2012. 

Objectives: To examine the cognitively protective effect of leisure and physical activities while accounting for prior cognitive ability, a rarely considered confounder of the previously reported associations between activity and cognitive aging. Participants: Community-dwelling sample of adults recruited into the Glostrup 1914 Cohort (baseline N = 802). All were born in 1914 and were assessed at ages 50, 60, 70, and 80. New participants were recruited during the study to counter attrition. Results: Greater activity (leisure or physical) was consistently associated with a higher level of cognitive ability. Adjusting for baseline cognitive ability (age 50) attenuated these associations, suggesting that associations between activity and cognition reported in old age are largely a consequence of preserved differentiation. A small but significant association remained between greater physical activity at age 60 or 70 and less cognitive decline. Conclusion: The association between more-frequent leisure activity and less cognitive decline mainly reflects the positive cross-sectional association between activity and cognition, although the link that remains between greater physical activity and a more-successful cognitive aging trajectory is of particular relevance to those who are developing interventions.

see full article

Additive interaction in survival analysis: use of the additive hazards model. Rod NH, Lange T, Andersen I, Marott JL, Diderichsen F. Epidemiology 23: 733-737, 2012. 

It is a widely held belief in public health and clinical decision-making that interventions or preventive strategies should be aimed at patients or population subgroups where most cases could potentially be prevented. To identify such subgroups, deviation from additivity of absolute effects is the relevant measure of interest. Multiplicative survival models, such as the Cox proportional hazards model, are often used to estimate the association between exposure and risk of disease in prospective studies...

See full abstract

Amniotic Fluid Chemokines and Autism Spectrum Disorders: An Exploratory Study Utilising a Danish Historic Birth Cohort. Abdallah MW, Larsen N, Grove J, Nørgaard-Pedersen B, Thorsen P, Mortensen EL, Hougaard DM. Brain, Behavior, and Immunity 26: 170-176, 2012.

Elevated levels of chemokines have been reported in plasma and brain tissue of individuals with Autism Spectrum Disorders (ASD). The aim of this study was to examine chemokine levels in amniotic fluid (AF) samples of individuals diagnosed with ASD and their controls. A Danish Historic Birth Cohort (HBC) kept at Statens Serum Institute, Copenhagen was utilized. Using data from Danish nation-wide health registers, a case-control study design of 414 cases and 820 controls was adopted...

See full abstract

Amniotic Fluid Inflammatory Cytokines: Potential Markers of Immunologic Dysfunction in Autism Spectrum Disorders. Abdallah MW, Larsen N, Grove J, Nørgaard-Pedersen B, Thorsen P, Mortensen EL, Hougaard DM. World Journal of Biological Psychiatry, Dec 19 2011. Objectives. 

The aim of the study was to analyze cytokine profiles in amniotic fluid (AF) samples of children developing autism spectrum disorders (ASD) and controls, adjusting for maternal autoimmune disorders and maternal infections during pregnancy. Methods. AF samples of 331 ASD cases and 698 controls were analyzed for inflammatory cytokines using Luminex xMAP technology utilizing a historic birth cohort. Clinical data were retrieved from nationwide registers, and case-control differences in AF cytokine levels were assessed using chi-square tests, logistic and tobit regression models.

See full abstract

Amniotic Fluid MMP-9 and Neutrophins in Autism Spectrum Disorders: An exploratory study. Abdallah MW, Pearce BD, Larsen N, Greaves-Lord K, Nørgaard-Pedersen B, Mortensen EL, Hougaard DM, Grove J. Autism Research. Dec 5: 428-433, 2012 

Evidence suggests that some developmental disorders, such as autism spectrum disorders (ASDs), are caused by errors in brain plasticity. Given the important role of matrix metalloproteinases (MMPs) and neurotrophins (NTs) in neuroplasticity, amniotic fluid samples for 331 ASD cases and 698 frequency-matched controls were analyzed for levels of MMP-9, brain-derived neurotrophic factor, NT-4 and transforming growth factor-β utilizing a Danish historic birth cohort and Danish nationwide health registers. Results showed elevated levels of MMP-9 in ASD cases compared with controls (crude and adjusted tobit regression P-values: 0.01 and 0.06)...

See full abstract

Are acceptance rates of a national preventive home visit programme for older people socially imbalanced? Yamada Y, Ekmann A, Nilsson CJ, Vass M, Avlund K: BMC Public Health 12: 396, doi: 10.1186/1471-2458-12-396., 2012. 

The purpose of this study is to investigate 1) whether socioeconomic status was associated with acceptance of preventive home visits among older people and 2) whether municipality invitational procedures for the preventive home visits modified the association. METHODS: The study population included 1,023 community dwelling 80-year-old individuals from the Danish intervention study on preventive home visits. Information on preventive home visit acceptance rates was obtained from questionnaires...

See full abstract

Cognitive Functions in Middle Aged Individuals are Related to Metabolic Disturbances and Aerobic Capacity: A Cross-sectional Study. Pedersen M, Pedersen KK, Bruunsgaard H, Krabbe KS, Thomsen C, Færch K, Pedersen BK, Mortensen EL. PLoS ONE 7(12): e51132. doi:10.1371/journal.pone.0051132, 2012. 

AIMS: Metabolic disturbances may contribute to cognitive dysfunction in patients with type 2 diabetes. We investigated the relation between cognitive impairment and metabolic deteriorations, low physical fitness, low-grade inflammation and abdominal obesity in middle aged individuals. METHODS: We conducted a cross-sectional study including 40 to 65 year-old patients with type 2 diabetes and limited co morbidity (N = 56), age-matched individuals with impaired glucose tolerance (N = 56) as well as age-matched controls with normal glucose tolerance (N = 72)...

See full abstract

Cortisol awakening response and negative emotionality linked to asymmetry in major limbic fibre bundle architecture. Madsen KS, Jernigan TL, Iversen P, Frokjaer VG, Mortensen EL, Knudsen GM, Baaré WFC: Psychiatry Research: Neuroimaging 201: 63-72, 2012. 

Here we tested the hypotheses that microstructural asymmetry of the major limbic fibre bundles would be associated with cortisol awakening response (CAR) and neuroticism, a personality trait associated with the tendency to experience negative emotions. Sixty-nine healthy adults were studied with diffusion-weighted imaging, and fractional anisotropy (FA) was extracted from the cingulum and uncinate fasciculus. Higher neuroticism scores, which were associated with higher CAR, were also correlated with higher right relative to left cingulum FA. Elevated CAR was associated with the degree of FA asymmetry within both the cingulum and the uncinate fasciculus, but in opposing directions...

see full abstract

Danish version of ‘The COPD self-efficacy scale’: Translation and psychometric properties.Emme C, Mortensen EL, Rydahl-Hansen S, Østergaard B, Phanareth K. Scandinavian Journal of Caring Sciences. 26: 615-623, 2012.

The aim of the study was to translate 'The COPD self-efficacy scale' (CSES) into Danish and to evaluate the psychometric properties of the Danish version (CSES-DK). CSES enables assessment of self-efficacy in individuals with chronic obstructive pulmonary disease (COPD). The scale consists of 34 items, describing situations which may cause dyspnoea in patients with COPD. The validity of the Danish version was evaluated by examining the associations between the CSES-DK score and socio-demographic variables (age, gender, education, disease severity and self-rated health). Factor analysis was conducted to compare the internal structure of the Danish version and the American source version. The study included 151 patients with COPD, recruited from three outpatient clinics...

See full abstract

Differential associations between white blood cell counts and fatigue in young and older adults. Avlund K, Hokland M, Mehlsen MY, Thomsen DK, Viidik A, Ekmann A, Zachariae R. Aging Clin Exp Res 24: 429-447, 2012. 

The aims of this exploratory study were to study whether fatigue might be related to the cellular immune system by 1) analysing if the number of white blood cell subsets are related to fatigue and 2) if possible relationships vary in younger and older community-dwelling individuals. METHODS: The participants were recruited from nine general practitioners in Aarhus County, Denmark and included 196 individuals aged 20-35 years and 314 individuals aged 70-85 years. The white blood cell counts included number of total leukocytes, lymphocytes, monocytes, neutrophils, eosinophils, and basophils. General fatigue was measured by a question from the SF-12 Vitality-Scale and mobility-related fatigue by the Avlund Mob-T Scale...

See full abstract

Different perspectives on the methodology of studying the potential effects of different alcohol drinking patterns in early pregnancy on the neuropsychological development of young children. Kesmodel US, Mortensen EL. BJOG 119:1673-1675, 2012.

Do early life characteristics influence cognitive function from young adulthood to middle-aged. Osler M, Avlund K, Mortensen EL. Eur J Public Health. Eur J Public Health. 2012 Oct 23. 

BACKGROUND: We examine the influence of social circumstances early in life on changes in cognitive function from young adulthood to middle age, and we explore the impact of birth characteristics, childhood activities, education and adult social class on the expected relationship. METHODS: A cohort of 11 532 men born in Copenhagen, Denmark in 1953-7906, 10 246 and 2483 participants-had completed assessments of cognitive function at ages 12, 18 and 57 years, respectively. Linear regression was used to investigate the association of early-life characteristics with cognitive test scores at these ages and with score changes from early to mid-adulthood. RESULTS: The cognitive scores at age 57 years had high correlations with scores at ages 12 (r = 0.67) and 18 years (r = 0.70), and these two scores also showed bivariate correlation (r = 0.69)...

see full abstract

Do negative social relations influence fatigue in middle aged Danish men?Ekmann A, Avlund K, Osler M, Lund R: J Psychosom Res. 73: 277-82, 2012. 

OBJECTIVE: Fatigue is a common complaint among young and old adults and may be associated with negative aspects of social relations. Hence, the purpose of this study was to explore the association between demands from and conflicts with different sources of social relations and fatigue. METHODS: The study was based on sub-populations of the 6292 members of the Danish Metropolit Cohort. The cohort comprises men born in 1953 in the Copenhagen Metropolitan area who participated in a questionnaire survey in 2004. Data were analysed using χ(2)-tests and multivariable logistic regression...

See full abstract

Does Binge Drinking During Early Pregnancy Increase the Risk of Psychomotor Deficits? Kesmodel US, Bay B, Wimberley T, Eriksen HLF, Mortensen EL. Alcoholism: Clinical and Experimental Research. Alcohol Clin Exp Res. 2013 Feb 15. 

BACKGROUND: The potential effects of binge drinking during pregnancy on child motor function have only been assessed in a few, small studies. We aimed to examine the effects of binge alcohol consumption during early pregnancy, including number of binge episodes and timing of binge drinking, on child motor function at age 5. METHODS: We performed a prospective follow-up study of 678 women and their children sampled from the Danish National Birth Cohort based on maternal alcohol consumption during pregnancy. At 5 years of age, the children were tested with the Movement Assessment Battery for Children.

see full abstract

Does fatigue predict non-fatal ischaemic heart disease and all cause mortality in middle aged Danish men?Ekmann A, Osler M, Avlund K. Psychosom Med. 74: 464-470, 2012.

Does shared family background influence the impact of educational differences on early mortality? Søndergaard G, Mortensen LH, Nybo Andersen AM, Andersen PK, Dalton SO, Madsen M, Osler M: Am J Epidemiol. 15;176: 675-683, 2012. 

The mechanisms behind social differences in mortality rates have been debated. The authors examined the extent to which shared family background and health in early life could explain the association between educational status and all-cause mortality rates using a sibling design. The study was register-based and included all individuals born in Denmark between 1950 and 1979 who had at least 1 full sibling born in the same time period (n = 1,381,436). All individuals were followed from 28 years of age until death, emigration, or December 2009...

See full abstract

Early motor developmental milestones and level of neuroticism in young adulthood. A 23-year follow-up study of the Copenhagen Perinatal Cohort. Flensborg-Madsen T, Sørensen HJ, Revsbech R, Mortensen EL. Psychological Medicine. Sept 2012. 

This study is the first to investigate associations between early motor developmental milestones and neuroticism in adulthood. Method Mothers of 9125 children of the Copenhagen Perinatal Cohort recorded 12 developmental milestones during the child's first year of life. A subsample of the cohort comprising 1182 individuals participated in a follow-up when they were aged 20-34 years and were administered the Eysenck Personality Questionnaire (EPQ). Associations between motor developmental milestones and level of neuroticism, extraversion and psychoticism were analysed by multiple linear regression adjusting for for sex, single-mother status, parity, mother's age, father's age, parental social status and birth weight...

See full abstract

Education and risk of coronary heart disease: assessment of mediation by behavioral risk factors using the additive hazards model. Nordahl H, Rod NH, Frederiksen BL, Andersen I, Lange T, Diderichsen F, Prescott E, Overvad K, Osler M. Eur J Epidemiol. 2013 Feb;28(2):149-57. 

Educational-related gradients in coronary heart disease (CHD) and mediation by behavioral risk factors are plausible given previous research; however this has not been comprehensively addressed in absolute measures. Questionnaire data on health behavior of 69,513 participants, 52 % women, from seven Danish cohort studies were linked to registry data on education and incidence of CHD. Mediation by smoking, low physical activity, and body mass index (BMI) on the association between education and CHD were estimated by applying newly proposed methods for mediation based on the additive hazards model, and compared with results from the Cox proportional hazards model...

see full abstract

Endurance training per se increases metabolic health in overweight men, a randomized controlled trial. Nordby P, Auerbach PL, Rosenkilde M, Kristiansen L, Thomasen JR, Rygaard L, Groth R, Brandt N, Helge JW, Richter EA, Ploug T, Stallknecht BM. Obesity 20(11): 2202-2212, 2012. 

Health benefits of physical activity may depend on a concomitant weight loss. In a randomized, controlled trial, we compared the effects of endurance training with or without weight loss to the effect of weight loss induced by an energy-reduced diet in 48 sedentary, moderately overweight men who completed a 12-week intervention program of training (T), energy-reduced diet (D), training and increased diet (T-iD), or control (C). An energy deficit of 600 kcal/day was induced by endurance training or diet in T and D and a similar training regimen plus an increased dietary intake of 600 kcal/day defined the T-iD group. Primary end point was insulin sensitivity as evaluated by HOMA-IR (mainly reflecting hepatic insulin sensitivity) and hyperinsulinemic, isoglycemic clamps (primarily reflecting peripheral insulin sensitivity)...

see full abstract

Effect of Chronic Escitalopram versus Placebo on Personality Traits in Healthy First-Degree Relatives of Patients with Depression: A Randomized Trial. Knorr U, Vinberg M, Mortensen EL, Winkel P, Gluud C, Wetterslev J, Gether U, Kessing LV. PLoS ONE 7(2): e31980. doi:10.1371/journal.pone.0031980, 2012. 

The present trial is the first to test the hypothesis that escitalopram may reduce neuroticism in healthy first-degree relatives of patients with major depressive disorder (MD). METHODS: The trial used a randomized, blinded, placebo-controlled parallel-group design. We examined the effect of four weeks escitalopram 10 mg daily versus matching placebo on personality in 80 people who had a biological parent or sibling with a history of MD. RESULTS: When compared with placebo, escitalopram did not significantly affect self-reported NEO-PI-R and EPQ neuroticism and extroversion, EPQ psychoticism, NEO-PI-R openness, or NEO-PI-R conscientiousness (p all above 0.05). However, escitalopram increased NEO-PI-R agreeableness scores significantly compared with placebo...

see full abstract

see full article

Effects of Nordic walking on cardiovascular risk factors in overweight individuals with type 2 diabetes, impaired or normal glucose tolerance. Fritz T, Caidahl K, Krook A, Lundström P, Mashili F, Osler M, Szekeres FL, Ostenson CG, Wändell P, Zierath JR. Diabetes Metab Res Rev. E-pub ahead of print, 2012. 

The effects of Nordic walking on cardiovascular risk factors were determined in overweight individuals with normal or disturbed glucose regulation. METHODS: We included 213 individuals, aged 60 ± 5.3 years and with body mass index (BMI) of 30.2 ± 3.8 kg/m(2); of these, 128 had normal glucose tolerance (NGT), 35 had impaired glucose tolerance (IGT) and 50 had type 2 diabetes mellitus (T2DM). Participants were randomized to unaltered physical activity or to 5 h per week of Nordic walking with poles, for a 4-month period. Dietary habits were unaltered. RESULTS: More cardiovascular risk factors were improved after exercise intervention in people with NGT compared with those with IGT or T2DM. Exercise capacity improved significantly in all three groups of participants who reported at least 80% compliance with the scheduled exercise. CONCLUSIONS: Nordic walking improved anthropometric measurements and exercise capacity. However, unsupervised Nordic walking may not provide a sufficient increase in exercise intensity to achieve ultimate health-promoting benefits on the cardiovascular parameters assessed in this study, particularly for those with disturbed glucose regulation...

see full abstract

Effects of tobacco smoking in pregnancy on offspring intelligence at the age of 5. Eriksen H-LF, Kesmodel US, Underbjerg M, Kilburn TR, Mortensen EL. Journal of Pregnancy. E-pub ahead of print. ArticleID945196,doi:10.1155/2012/945196, 2012.

The aim of the study was to examine the effects of tobacco smoking in pregnancy on children's IQ at the age of 5. A prospective follow-up study was conducted on 1,782 women, and their offspring were sampled from the Danish National Birth Cohort. At 5 years of age, the children were tested with the Wechsler Preschool and Primary Scale of Intelligence-Revised. Parental education, maternal IQ, maternal alcohol consumption in pregnancy, the sex and age of the child, and tester were considered core confounders, but the full model also controlled for prenatal paternal smoking, maternal age and Bodymass Mass Index, parity, family/home environment, postnatal parental smoking, breast feeding, the child's health status, and indicators for hearing and vision impairments...

see full abstract

Evidence based physiotherapy guidelines for prevention of falls and fall injuries (In Finnish). Piirtola M, Pajala S, Karinkanta S, Mänty M, Pitkänen T, Punakallio A, Sihvonen S, Kettunen J, Kangas H. Fysioterapia (physiotherapy) 1: 12-17, 2012.

Fatigability in basic indoor mobility in nonagenarians. Mänty M, Ekmann A, Thinggaard M, Christensen K, Avlund K. J Am Geriatr Soc. 60: 1279-1285, 2012. 

OBJECTIVES: To evaluate the prevalence and associated health factors of indoor mobility-related fatigability in nonagenarians. DESIGN: A cross-sectional observational study of all Danes born in 1905 and assessed in 1998. SETTING: Community, sheltered housing and nursing homes. PARTICIPANTS: Individuals aged 92 and 93 (N = 1,181) who were independent of help in basic indoor mobility. MEASUREMENTS: Fatigability in basic indoor mobility was defined as a subjective feeling of fatigue when transferring or walking indoors...

see full abstract

Fatigue and depressive symptoms. Mänty M, Rantanen T, Era P, Avlund K. Journal of Applied Gerontology. In press, 2012.

The purpose of this study is to describe the prevalence of depressive symptoms among community-dwelling older adults reporting mobility-related or general feelings fatigue. The study population consisted of 75-year-old community-living individuals (n = 561). Both, mobility-related and general fatigue, were associated in a stepwise relationship with depressive symptoms: a higher level of fatigue was related to higher level of depressive symptoms. Especially major general fatigue was strongly associated with high level of depressive symptoms. It is importantfor professionals of the field to be aware of the associations between different measures of fatigue and depressive symptoms.

See full text

Fatigue, general health and ischemic heart disease in older adults.Ekmann A, Petersen I, Mänty M, Christensen K, Avlund K. J Gerontol Med Sci. E-pub ahead of press, 2012. 

The aim of this study was to investigate the predictive value of fatigue for IHD and general health in nondisabled individuals free of cardiovascular disease and older than 70 years. METHODS: The study population was drawn from The Longitudinal Study of Aging Danish Twins. In total, 1,696 participants were followed up for 2-10 years by questionnaires and 10-16 years through registries. Kaplan Meier, Cox Proportional Hazard and logistic regression were used to analyze data...

See full abstract

Fish,n-3 Fatty Acids, and Cardiovascular Diseases in Women of Reproductive Age: A Prospective Study in a Large National Cohort. Strøm M, Halldorsson TI, Mortensen EL, Torp-Pedersen C, Olsen SF. Hypertension 59:36-43, 2012. 

The aim of this study was to explore the association between intake of LCn3FAs and the risk of cardiovascular disease in a large prospective cohort of young women (mean age at baseline: 29.9 years [range: 15.7-46.9]). Exposure information on 48 627 women from the Danish National Birth Cohort was linked to the Danish National Patients Registry for information on events of hypertensive, cerebrovascular, and ischemic heart disease used to define a combined measure of cardiovascular diseases...

See full abstract

Formal home help services and institutionalisation. Yamada Y, Siersma V, Avlund K, Vass M: Arch Geriatr Gerontol. 60: e52-56, 2012. 

The effect of home help services has been inconsistent. Raising the hypothesis that receiving small amounts of home help may postpone or prevent institutionalization, the aim of the present study is to analyze how light and heavy use of home help services was related to the risk for institutionalization. The study was a secondary analysis of a Danish intervention study on preventive home visits in 34 municipalities from 1999 to 2003, including 2642 home-dwelling older people who were nondisabled and did not receive public home help services at baseline in 1999 and who lived at home 18 months after baseline...

See full abstract

Forty-Five year Mortality Rate as a Function of the Number and Type of Psychiatric Diagnoses Found in a Large Danish Birth Cohort. Madarasz W, Manzardo A, Mortensen EL, Penick E, Knop J, Sørensen HJ, Becker U, Nickel E, Gabrielli WJR. Canadian Journal of Psychiatry 57: 505-511, 2012. 

OBJECTIVE: Psychiatric comorbidities are common among psychiatric patients and typically associated with poorer clinical prognoses. Subjects of a large Danish birth cohort were used to study the relation between mortality and co-occurring psychiatric diagnoses.METHOD: We searched the Danish Central Psychiatric Research Registry for 8109 birth cohort members aged 45 years. Lifetime psychiatric diagnoses (International Classification of Diseases, Revision 10, group F codes, Mental and Behavioural Disorders, and one Z code) for identified subjects were organized into 14 mutually exclusive diagnostic categories. Mortality rates were examined as a function of number and type of co-occurring diagnoses. RESULTS: Psychiatric outcomes for 1247 subjects were associated with 157 deaths...

see full abstract

Health Impact Assessment of increased cycling to place of work or education in Copenhagen. Holm AL, Glümer C, Diderichsen F. BMJ Open 24; 2(4). doi:pii: e001135. 10.1136/bmjopen-2012-001135, 2012. 

OBJECTIVE: To quantify the effects of increased cycling on both mortality and morbidity. POPULATION: Effects were calculated based on the working-age population of Copenhagen. MAIN OUTCOME MEASURES: The primary outcome measure was change in burden of disease (measured as disability-adjusted life years (DALY)) due to changed exposure to the health determinants physical inactivity, air pollution (particulate matter

see full abstract

see full text

Health, work, and personal-related predictors of time to return to work among employees with mental health problems. Nielsen MB, Bültmann U, Madsen IE, Martin M, Christensen U, Diderichsen F, Rugulies R. Disabil Rehabil. 34(15): 1311-6, 2012. 

PURPOSE: To identify health-, personal- and work-related factors predictive of return to work (RTW) in employees sick-listed due to common mental health problems, such as, stress, depression, burnout, and anxiety. METHODS: We distributed a baseline questionnaire to employees applying for sickness absence benefits at a large Danish welfare Department (n = 721). A total of 298 employees returned the questionnaire containing information on possible predictors of RTW...

see full abstract

Impact of social capital on 8 year mortality among older people in 34 Danish municipalities. Poulsen T, Siersma VD, Lund R, Christensen U, Vass M, Avlund K: J Aging Health 24: 1203-22, 2012. 

OBJECTIVE: To analyze the impact of social capital measures (bonding, bridging, and linking) on all-cause mortality at 8-year follow-up among older people aged 75 and 80 at baseline. METHOD: Prospective cohort study on preventive home visits including 2,863 seventy-five-year-olds and 1,171 eighty-year-olds in 34 Danish municipalities. The associations of the three aspects of social capital measures with mortality were tested in Cox regression models on time to death...

See full abstract

Improving a measure of mobility-related fatigue (the Mob-T Scale) by establishing item intensity. Fieo R, Mortensen EL, Rantanen T, Avlund K. J Am Geriatr Soc. In press, 2012. 

OBJECTIVES: To improve the construct validity of self-reported fatigue by establishing a formal hierarchy of scale items and to determine whether such a hierarchy could be maintained across time (aged 75-80), sex, and nationality...

see full abstract

Improving personality facet scores with multidimensional computer adaptive testing: An illustration with the NEO PI-R. Assessment. Makransky G, Mortensen EL, Glas CAW. Assessment. 2013 Feb;20(1):3-13. doi: 10.1177/1073191112437756. Epub 2012 Feb 21. 

This article investigates the possibility of increasing the precision of the NEO PI-R facet scores by scoring items with multidimensional item response theory and by efficiently administering and scoring items with multidimensional computer adaptive testing (MCAT). The increase in the precision of personality facet scores is obtained from exploiting the correlations between the facets. Results indicate that the NEO PI-R could be substantially shorter without attenuating precision when the MCAT methodology is used. Furthermore, the study shows that the MCAT methodology is particularly appropriate for constructs that have many highly correlated facets...

see full abstract

Increasing work-time influence: consequences for flexibility, variability, regularity and predictability. Nabe-Nielsen K, Garde AH, Aust B, Diderichsen F: Ergonomics 55. 440-449, 2012. 

This quasi-experimental study investigated how an intervention aiming at increasing eldercare workers' influence on their working hours affected the flexibility, variability, regularity and predictability of the working hours. We used baseline (n = 296) and follow-up (n = 274) questionnaire data and interviews with intervention-group participants (n = 32). The work units in the intervention group designed their own intervention comprising either implementation of computerised self-scheduling (subgroup A), collection of information about the employees' work-time preferences by questionnaires (subgroup B), or discussion of working hours (subgroup C)...

see full abstract

Infections during pregnancy and after birth and risk of autism spectrum disorders: a register-based study utilizing a Danish historic birth cohort. Abdallah MW, Hougaard DM, Nørgaard-Pedersen B, Grove J, Bonefeld-Jørgensen EC, Mortensen EL. Turkish Journal of Psychiatry. 23: 229-236, 2012. 

OBJECTIVE: Mounting evidence suggests that immune dysfunction may play a crucial role in the pathophysiology of autism spectrum disorders (ASD). In addition, several studies have reported that congenital and postnatal infections may contribute to the neurobiological basis of ASD. This study aimed to investigate the relationship between infections during pregnancy and after birth, and ASD...

See Full abstract

Intake of dairy products in relation to periodontitis in older adults. Adegboye ARA, Christensen LB, Holm-Pedersen, Avlund K, Boucher BJ, Heitmann BL. Nutrients 4: 1219-29, Sept 4, 2012. 

This cross-sectional study investigates whether calcium intakes from dairy and non-dairy sources, and absolute intakes of various dairy products, are associated with periodontitis. The calcium intake (mg/day) of 135 older Danish adults was estimated by a diet history interview and divided into dairy and non-dairy calcium. Total dairy foods (IRR = 0.96; p = 0.003), milk (IRR = 0.96; p = 0.028) and fermented foods intakes (IRR = 0.97; p = 0.029) were associated with reduced risk of periodontitis, but cheese and other dairy foods intakes were not. These results suggest that dairy calcium, particularly from milk and fermented products, may protect against periodontitis. Prospective studies are required to confirm these findings...

See full abstract

Interactive effects of social support and disclosure on fertility-related stress. Martins MV, Peterson BD, Costa P, Costa ME, Lund R, Schmidt L: Journal of Social and Personal Relationships. DOI: 10.1177/0265407512456672, 2012. 

The present study aimed to examine the role of disclosure of fertility status in moderating the relationship between perceived social support and fertility-related stress. The study population (N = 698) was drawn from a longitudinal cohort design of Danish men and women beginning fertility treatment with a 12-month follow-up. Participants were 698 subjects (364 women and 334 men) who completed self-administered questionnaires measuring perceived social support at T1, and fertility status disclosure and fertility stress at T2. Results indicated that when infertility is not disclosed to at least a close relationship...

see full abstract

see full text

Life time occupational physical activity and musculoskeletal ageing in middle-aged men and women in Denmark. Retrospective Cohort Study Protocol and Methods. Møller A, Mortensen OS, Reventlow S, Skov PG, Andersen JH, Rubak TS, Hansen ÅM, Andersen LL, Lund R, Osler M, Christensen U, Avlund K. JMIR Research Protocols 1, 2:7, 2012. 

Objective: The aim of this study is to examine the influence of lifetime occupational physical activity on physical function in midlife. The study follows the “occupational life-course perspective,” emphasizing the importance of occupational exposures accumulated throughout life on the musculoskeletal aging process taking socioeconomic and lifestyle factors into consideration. Methods: This study is a retrospective cohort study including a cross-sectional measurement of physical function in 5000 middle-aged Danes. Data was obtained from the Copenhagen Aging and Midlife Biobank (CAMB) which is based on three existing Danish cohorts...

See full abstract

Long-term Gynecological Outcomes in Women with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency. Johannsen TH, Ripa CPL, Carlsen E, Starup J, Nielsen OH, Schwartz M, Drzewiecki KT, Mortensen EL, Main KM: International Journal of Pediatric Endocrinology. In press, 2012. 

Background. Our knowledge on long-term outcome in CAH remains incomplete. Methods. In a prospective study (33CAH patients, 33 age-matched controls), reproductive outcomes, self-rating of genital appearance and function, and sexuality were correlated to degree of initial virilisation, genotype, and surgery...

see full abstract

see full text

Low to moderate alcohol intake during pregnancy and risk of psychomotor deficits. Bay B, Støvring H, Wimberley T, Denny CH, Mortensen EL, Eriksen H-LF, Kesmodel US. Alcoholism: Clinical and Experimental Research. 36: 807-814, 2012. 

BACKGROUND: To examine the effects of low to moderate alcohol consumption during pregnancy on child motor function at age 5. METHODS: A prospective follow-up study of 685 women and their children sampled from the Danish National Birth Cohort based on maternal alcohol consumption during pregnancy. At 5 years of age, the children were tested with the "Movement Assessment Battery for Children" (MABC). Parental education, maternal IQ, prenatal maternal smoking, the child's age at testing, and gender of child were considered core confounders, while the full model also controlled for prenatal maternal binge drinking episodes, age, maternal prepregnancy body mass index, parity, home environment, postnatal parental smoking, health status, and indicators for hearing and vision impairment...

See full abstract

Mental vulnerability as a risk factor for depression: a prospective cohort study in Denmark. Østergaard D, Dalton SO, Bidstrup PE, Poulsen AH, Frederiksen K, Eplov LF, Johansen C, Mortensen EL: International Journal of Social Psychiatry 58: 306-314, 2012. 

This study investigated whether mental vulnerability is associated with hospitalization for depression. METHODS: A prospective study was conducted of six cohorts from the population of Copenhagen County, Denmark, with baseline information on mental vulnerability, lifestyle, social factors and comorbidity collected in 1976, 1982-84, 1991 and 1997-98 (N = 11,862). By register-linkage information on hospital contacts for affective disorders were obtained from the Danish Psychiatric Central Register...

See full abstract

Mobility decline in old age. Rantakokko M, Mänty M, Rantanen T: Exerc Sport Sci Revf. Exerc Sport Sci Rev. 2013 Jan;41(1):19-25. 

Mobility is important for community independence. With increasing age, underlying pathologies, genetic vulnerabilities, physiological and sensory impairments, and environmental barriers increase the risk for mobility decline. Understanding how mobility declines is paramount to finding ways to promote mobility in old age...

See full abstract

Mobility-related fatigue, walking speed and muscle strength in older people. Mänty M, Mendes de Leon C, Rantanen T, Era P, Pedersen AN, Ekmann A, Schroll M, Avlund K. J Gerontol Med Sci. 67A: 523-529, 2012. 

The purpose of the present study was to examine the association between mobility-related fatigue and walking speed and to test the degree to which muscle strength accounts for this association. METHODS: The study is based on baseline (n = 523) and 5-year follow-up data (n = 292) from a cohort of 75-year-old persons. Standardized assessments include self-report measures of mobility-related fatigue (score range 0-6) and medical history, as well as performance-based assessment of walking speed and maximal isometric strength of knee extension, body extension, and handgrip...

see full abstract

Neonatal chemokine levels and risk of autism spectrum disorders: Findings from a Danish historic birth cohort follow-up study. Abdallah MW, Larsen N, Grove J, Bonefeld-Jørgensen EC, Nørgaard-Ped¬ersen B, Hougaard DM, Mortensen EL. Cytokine, Dec 2012. 

A potential role of chemokines in the pathophysiology of Autism Spectrum Disorders (ASDs) has been previously suggested. In a recent study we examined levels of three inflammatory chemokines (MCP-1, MIP-1α and RANTES) in samples of amniotic fluid of children diagnosed later in life with ASD and controls frequency-matched to cases on gender and year of birth. In this follow-up study, levels of the same chemokines were analyzed postnatally in dried blood spot samples from the same subjects utilizing the Danish Newborn Screening Biobank. Crude estimates showed decreased levels of RANTES. In the adjusted estimates, no differences were found in levels of the three examined chemokines in ASD cases compared to controls...

See full abstract

Neonatal levels of cytokines and risk of autism spectrum disorders: An exploratory register-based historic birth cohort study utilizing the Danish Newborn Schreening Biobank. Abdallah MW, Larsen N, Mortensen EL, Atladottir HO, Nørgaard-Pedersen B, Bonefeld-Jørgensen EC, Grove J, Hougaard DM. Journal of Neuroimmunology 252: 75-82, 2012. 

The aim of the study was to analyze cytokine profiles in neonatal dried blood samples (n-DBSS) retrieved from The Danish Newborn Screening Biobank of children developing Autism Spectrum Disorders (ASD) later in life and controls. Samples of 359 ASD cases and 741 controls were analyzed using Luminex xMAP technology and clinical data were retrieved from nationwide registers...

See full abstract

Neonatal Levels of Neurotrophic Factors and Risk of Autism Spectrum Disorders. Abdallah MW, Mortensen EL, Greaves-Lord K, Larsen N, Bonefeld-Jørgensen EC, Nørgaard-Pedersen B, Hougaard DM, Grove J: Acta Psychiatrica Scandinavica. Oct 5, 2012. 

OBJECTIVE: To examine levels of 3 neurotrophic factors (NTFs): Brain derived neurotrophic factor (BDNF), Neurotrophin-4 (NT-4), and transforming growth factor-β (TGF-β) in dried blood spot samples of neonates diagnosed with autism spectrum disorders (ASD) later in life and frequency-matched controls. METHOD: Biologic samples were retrieved from the Danish Newborn Screening Biobank. NTFs for 414 ASD cases and 820 controls were measured using Luminex technology. Associations were analyzed with continuous measures (Tobit regression) as well as dichotomized at the lower and upper 10th percentiles cutoff points derived from the controls' distributions (logistic regression)...

See Full Abstract

Occupational characteristics and cognitive aging in the Glostrup 1914 cohort. Gow A, Avlund K, Mortensen EL. J Gerontol Psych Sci. E-pub ahead of print, 2012.

The effect of occupational characteristics on cognitive change over 20 years was examined. METHOD: 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 cognitive ability tests at ages 60, 70, and 80. RESULTS: Individuals in more intellectually challenging occupations had higher cognitive ability (r = .27-.38, p < .01), whereas those in more physically hazardous occupations performed more poorly (r = -.12 and -.13 at ages 50 and 60, p < .05). In growth curve models, intellectual challenge continued to be associated with cognitive ability, controlling for sex, education, and social class. However, the association was reversed after accounting for cognitive ability at age 50; of 2 individuals with the same baseline level of cognitive ability, the one in the more intellectually challenging occupation had lower subsequent cognitive ability...

see full abstract

Paid care work and depression: a longitudinal study of antidepressant treatment in female eldercare workers before and after entering their profession. Madsen IE, Aust B, Burr H, Carneiro IG, Diderichsen F, Rugulies R. Depress Anxiety 29: 605-13, 2012. 

We examined prevalences of antidepressant purchases during 1995-2008 in a cohort of female eldercare workers who entered their profession in 2004 (n = 1,946). These yearly prevalences were compared to those of a representative sample of the female Danish working population (n = 4,201). Trends in antidepressants prevalences were examined using generalized estimation equations. Further, to account for bias by treatment seeking, we compared self-reported depressive symptoms in 2005 measured by the mental health scale from the SF-36. Female eldercare workers had consistently higher prevalence of antidepressant treatment than the general female working population...

see full abstract

Perceived barriers in the outdoor environment and development of walking difficulties in older people. Rantakokko M, Iwarsson S, Mänty M, Leinonen R, Rantanen T: Age and Ageing 41: 118-121, 2012. 

The aim of the study reported in this letter was to explore whether perceived barriers in the outdoor environment predict development of difficulties in advanced and basic mobility among community-dwelling people who did not have walking difficulties at baseline.

Perceived stress and risk of adult-onset asthma and other atopic disorders: a longitudinal cohort study. Rod NH, Kristensen TS, Lange P, Prescott E, Diderichsen F. Allergy 67: 1408-14, 2012. 

Psychological stress can affect airway inflammatory response to irritants and allergens, but the importance of stress in the etiology of adult-onset respiratory and dermatologic allergic disorders remains unclear. We aim to address the relationship between perceived stress and the risk of adult-onset asthma, allergic rhinitis, atopic dermatitis, and asthma/bronchitis medication...

See full abstract

Periodontal inflammation in relation to cognitive function in an older Danish population. Kamer AR, Morse D, Holm-Pedersen P, Mortensen EL, Ellefsen B, Avlund K. Journal of Alzheimer’s Disease 28: 613-624, 2012. 

We hypothesized that older adults with periodontal inflammation (PI) or many missing teeth would show impaired cognition compared to subjects without PI or with few missing teeth, and among subjects with PI, those with many missing teeth would show impaired cognition compared to those with few missing teeth. The effect of PI/tooth loss on cognitive function [measured by Digit Symbol (DST) and Block Design (BDT) tests] was assessed in 70-year old Danish subjects...

See full abstract

Predisposition to Obesity: Should We Target Those Most Susceptible. Olsen NJ, Mortensen EL, Heitmann BL. Current Obesity Report 1: 35-41, 2012. 

The purpose of this paper is to review interventions on obesity prevention published during the past year, and to examine if interventions targeting predisposed groups or individuals seem more efficient in preventing obesity than studies targeting general populations. Among 15 identified studies, 7 targeted predisposed children or adolescents. More of the studies targeting predisposed individuals were able to show significant effects than the studies targeting general populations. Most studies targeting predisposed defined the predisposition based on ethnicity or socioeconomic status. Thus, we may be more successful in preventing obesity when targeting predisposed individuals, but more studies are needed before a firm conclusion can be drawn...

see full abstract

Premorbid intelligence and educational level in bipolar and unipolar disorder: A Danish draft board study. Sørensen HJ, Sæbye D, Urfer-Parnas A, Mortensen EL, Parnas J. Journal of Affective Disorders 136: 1188-91, 2012. 

BACKGROUND: Registry-based studies have found no or weak associations between premorbid intelligence and the broad entity of affective spectrum disorder, but none of the studies compared bipolar/unipolar subgroups. METHODS: IQ and educational level were assessed at the draft board, and hospital diagnoses were followed up to the ages 43-54 years for 294 individuals hospitalized with bipolar disorder and 1434 with unipolar or depressive disorder. Controls comprised 20,531 individuals without psychiatric registration...

See full abstract

Premorbid Multivariate Markers of Neurodevelopmental Instability in the Prediction of Adult Schizophrenia-Spectrum Disorder: A High-Risk Prospective Investigation. Golembo-Smith S, Schiffman J, Kline E, Sorensen HJ, Mortensen EL, Stapleton L, Hayashi K, Michelsen NM, Ekstrom M, Mednick S. Schizophrenia Research 139: 129-135, 2012.

The authors examined whether multiple childhood indicators of neurodevelopmental instability known to relate to schizophrenia-spectrum disorders could predict later schizophrenia-spectrum outcomes. A standardized battery of neurological and intellectual assessments was administered to a sample of 265 Danish children in 1972, when participants were 10-13 years old. Parent psychiatric diagnoses were also obtained in order to evaluate the predictive strength of neurodevelopmental factors in combination with genetic risk. Participants were grouped into three categories indicating level of genetic risk. Results suggest that, with replication, multivariate premorbid prediction could potentially be a useful complementary approach to identifying individuals at risk for developing a schizophrenia-spectrum disorder. Genetic risk, MPAs, and other markers of neurodevelopmental instability may be useful for comprehensive prediction models...

see full abstract

Relation of Frontal D2/3 Binding Potentials to Cognition: A Study of Antipsychotic-Naive Schizophrenia Patients. Fagerlund B, Pinborg LH, Mortensen EL, Friberg L, Baaré WFC, Gade A, Svarer C, Glenthøj BY. The International Journal of Neuropsychopharmacology. In press, 2012. 

The objective was to examine this relation in the frontal cortex in first-episode, drug-naive schizophrenia patients. Based on preclinical and pharmacological evidence, we specifically expected to find a relation between D(2/3) receptor binding potentials and set shifting. This was a cross-sectional, case-control study using single-photon emission computerized tomography with the D(2/3)-receptor ligand [(123)I]epidepride, co-registered with structural magnetic resonance imaging and correlated to cognitive measures. The main findings indicated a relation between D(2/3) receptor binding in the frontal cortex and set shifting, planning and attention, but also support a differential involvement of cortical dopamine D(2/3) receptor binding in at least some cognitive functions, perhaps particularly attention, in schizophrenia patients compared to healthy people...

See Full Abstract

Social and psychological predictors of onset of anxiety disorders: results from a large prospective cohort study.Flensborg-Madsen T, Tolstrup J, Sørensen HJ, Mortensen EL. Social Psychiatry and Psychiatric Epidemiology. 47: 711-721, 2012. 

The purpose of the study was to investigate in a prospective longitudinal study whether social and psychological factors are associated with the later risk of being admitted to a hospital and receive a diagnosis of anxiety disorders. The study population comprised 4,497 members of The Copenhagen Perinatal Cohort (CPC) who in 1993 answered a mailed questionnaire containing questions on a range of social and psychological factors. In 2007, the study population was linked to The Danish Hospital Discharge Register and the Danish Psychiatric Central Register to obtain information on registration with anxiety disorders. A total of 5.3% of the study population had lifetime registration with an anxiety disorder diagnosis. The risk of admission for anxiety disorders was significantly associated with previous: discontentedness with partner-status, loneliness, self-rated low intelligence, not feeling part of a whole, unhappiness, low quality of life, and low meaningfulness...

see full abstract

Social inequality in dynamic balance performance in an early old age Spanish population: the role of health and life style associated factors. Lopez SR, Nilsson CJ, Lund RL, Lopez PM, Fernández-Ballesteros R, Avlund K: Arch Gerontol Geriatr. 43: e139-45, 2012. 

This study investigates the association between socioeconomic status (SES) and dynamic balance performance and whether lifestyle factors explained any possible associations. A total of 448 nondisabled individuals, age-range 54-75 years and enrolled in the Active Aging Longitudinal Study of Spain in 2006, constituted the study population. Baseline data of this cross-sectional study were obtained by personal interviews and objective measures of balance performance...

see full abstract

Socioeconomic factors may influence the surgical technique for benign hysterectomy. Daugbjerg SB, Ottesen B, Diderichsen F, Frederiksen BL, Osler M. Dan Med J. 59: A4440, 2012. 

Owing to significantly improved outcomes, vaginal hysterectomy is the recommended standard approach when feasible in preference to abdominal hysterectomy. It is, however, not clear whether the use of vaginal hysterectomy varies with the women's socioeconomic background. All 22,150 women registered in the Danish Hysterectomy Database in the 2004-2008-period were included in this cohort study and linked to central registers providing information on education, income and employment. Analyses were carried out using multiple logistic regression models...

See full abstract

Socioeconomic position, treatment, and survival of non-Hodgkin lymphoma in Denmark - a nationwide study. Frederiksen BL, Dalton SO, Osler M, Steding-Jessen M, de Nully Brown P. Br J Cancer 28: 988-995, 2012. 

This study investigates several individual-level markers of socioeconomic position (SEP) in relation to NHL survival, and explores whether any social differences could be attributed to comorbidity, disease and prognostic factors, or the treatment given. METHODS: This registry-based cohort study links clinical data on prognostic factors and treatment from the national Danish lymphoma database to individual socioeconomic information in Statistics Denmark including 6234 patients diagnosed with NHL in 2000-2008. RESULTS: All-cause mortality was 40% higher in NHL patients with short vs higher education diagnosed in the period 2000-2004 (hazard ratio (HR)=1.40 (1.27-1.54)), and 63% higher in the period 2005-2008 (HR=1.63 (1.40-1.90)). Further, mortality was increased in unemployed and disability pensioners, those with low income, and singles...

See full abstract

See full text

The effect of alcohol binge drinking in early pregnancy on general intelligence in children. Kesmodel US, Eriksen H-LF, Underbjerg M, Kilburn TR, Støvring H, Wimberley T, Mortensen EL: BJOG 119: 1222-1231, 2012. 

OBJECTIVE: To examine the effects of binge alcohol consumption during early pregnancy, including the number of binge episodes and the timing of binge drinking, on general intelligence in 5-year-old children. POPULATION: A cohort of 1617 women and their children sampled from the Danish National Birth Cohort. METHODS: Participants were sampled on the basis of maternal alcohol consumption during pregnancy. At 5 years of age the children were tested with six subtests from the Wechsler Preschool and Primary Scale of Intelligence - Revised (WPPSI-R)...

See full abstract

The effects of low to moderate alcohol consumption and binge drinking in early pregnancy on behaviour in fiveyear old children. A prospective cohort study on 1628 children. Skogerbø Å, Kesmodel US, Denny CH, Kjaersgaard MIS, Wimberley T, Landrø NI, Mortensen EL: BJOG. In press, 2012. 

OBJECTIVE: To examine the effects of low to moderate maternal alcohol consumption and binge drinking in early pregnancy on behaviour in children at the age of 5 years...

See full abstract

The effects of low to moderate alcohol consumption and binge drinking in early pregnancy on executive function in five-year old children. Skogerbø Å, Kesmodel US, Wimberley T, Støvring H, Bertrand J, Landrø NI, Mortensen EL. BJOG 119: 1201-1210, 2012. 

OBJECTIVE: To conduct a combined analysis of the estimated effects of maternal average weekly alcohol consumption, and any binge drinking, in early to mid pregnancy on general intelligence, attention, and executive function in 5-year-old children. METHODS: Participants were sampled based on maternal alcohol consumption during early pregnancy. At age 5 years, the children were tested for general intelligence, attention, and executive function...

See full abstract

The effects of low to moderate prenatal alcohol exposure in early pregnancy on IQ in 5-year-old children. Eriksen H-LF, Mortensen EL, Kilburn T, Underbjerg M, Bertrand J, Støvring H, Wimberley T, Grove J, Kesmodel US. BJOG 119: 1191-1200, 2012. 

OBJECTIVE: To examine the effects of low to moderate maternal alcohol consumption during early pregnancy on children's intelligence (IQ) at age 5 years. METHODS: Participants were sampled based on maternal alcohol consumption during pregnancy. At 5 years of age, children were tested with the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R). Parental education, maternal IQ, maternal smoking in pregnancy, the child's age at testing, gender, and tester were considered core confounding factors, whereas the full model also controlled for maternal binge drinking, age, BMI, parity, home environment, postnatal smoking in the home, health status, and indicators for hearing and vision impairments...

See full abstract

The Lifestyle during Pregnancy Study Group. The effect of different drinking patterns in early to mid-pregnancy on child’s intelligence, attention and executive function. Kesmodel US, Bertrand J, Støvring H, Skarpness B, Denny CH, Mortensen EL: BJOG 119: 1180-90, 2012. 

OBJECTIVE: To conduct a combined analysis of the estimated effects of maternal average weekly alcohol consumption, and any binge drinking, in early to mid pregnancy on general intelligence, attention, and executive function in 5-year-old children. POPULATION: A cohort of 1628 women and their children sampled from the Danish National Birth Cohort. METHODS: Participants were sampled based on maternal alcohol consumption during early pregnancy. At age 5 years, the children were tested for general intelligence, attention, and executive function...

see full abstract

Understanding the natural progression in %FEV1 decline in patients with cystic fibrosis: a longitudinal study. Taylor-Robinson D, Whitehead M, Diderichsen F, Olesen HV, Pressler T,Smyth RL, Diggle P: Thorax 67: 860-6, 2012. 

BACKGROUND: Forced expiratory volume in 1 s as a percentage of predicted (%FEV1) is a key outcome in cystic fibrosis (CF) and other lung diseases. As people with CF survive for longer periods, new methods are required to understand the way %FEV1 changes over time. An up to date approach for longitudinal modelling of %FEV1 is presented and applied to a unique CF dataset to demonstrate its utility at the clinical and population level. METHODS AND FINDINGS: The Danish CF register contains 70,448 %FEV1 measures on 479 patients seen monthly between 1969 and 2010. The variability in the data is partitioned into three components (between patient, within patient and measurement error) using the empirical variogram...

See full abstract

Use of clinical databases and central health registries for description of disease courses. Frederiksen BL, Mårtensson S, Nørgård BM, Johnsen SP, Osler M. Ugeskrift for Laeger 23: 1145-1149, 2012. 

In Denmark, the linkage between national clinical databases and central health administrative and socio-demographic registries provides unique opportunities for describing and analysing disease courses in ways that can be applied for quality improvement purposes, in the evaluation of new organisational initiatives, and for research. This status article presents an overview of the possibilities and discusses the potentials and challenges...

see full abstract

Validity and internal consistency of mobility scales for healthy older people in Germany. Bruhl A, Avlund K. J Clin Gerontol Geriatr. 3: 29-35, 2012.

Validity of workers’ self-reports. Evaluation of a question assessing lifetime exposure to occupational physical activity. Møller A, Reventlow S, Andersen JH, Avlund K, Mortensen OS. British Journal of Medicine and Medical Research. 2: 536-552, 2012. 

Aims: In epidemiological studies exposure assessment based on questionnaires is the most cost-effective method. A question about lifetime exposure to occupational physical activity (OPA) was used in a population-based survey (part of the Copenhagen Aging and Midlife Biobank, CAMB). The aim of the study was to validate this question through a three-step process. Methodology: Firstly, the response process was studied by cognitive interviewing of 7 persons. Secondly, 64 persons participated in semi-structured interviews about their work-life, and expert judgments of exposure to OPA were compared with questionnaire-data. Exposure was 20 years of work in one of four categories of OPA: sedentary, standing and walking, moderate or high OPA. Kappa values were calculated for agreement and interpreted according to Landis and Koch’s criteria. Agreement was visualized in Bland-Altman plots. Thirdly, intra- and inter-rater reliability of expert judgments was tested...

see full abstract

Widening social inequality in life expectancy in Denmark. A register-based study on social composition and mortality trends for the Danish population. Brønnum-Hansen H, Baadsgaard M. BMC Public Health 12: 994, 2012. 

The aim of the study was to estimate trends during a quarter of a century in social inequality in life expectancy and to compare results based on different social stratifications. METHODS: Life tables by sex and various levels of education and income were constructed for each year in the period 1987-2011 by linking individual data from nationwide registers comprising information on all Danish citizens on date of birth, date of death, education and income. Trends in life expectancies were compared for different categories of social grouping...

See full abstract

See full article

 Program 4 - Society and CultureTil toppen

Brugen af måleapparater i håndteringen af livsstilssygdomme i Danmark. Oxlund B. Tidsskrift for forskning i sygdom og samfund 17: 101-118, 2012.

Chronicity and Control: Framing ‘noncommunicable diseases’. Special issue ‘Medical anthropology in Europe: shaping the field’. Whyte SR. Anthropology & Medicine 19(1): 63-74, 2012. 

This paper proposes a way of framing the study of 'noncommunicable diseases' within the more general area of chronic conditions. Focusing on Africa, it takes as points of departure the situation in Uganda, and the approach to health issues developed by a group of European and African colleagues over the years. It suggests a pragmatic analysis that places people's perceptions and practices within a field of possibilities shaped by policy, health care systems, and life conditions. In this field, the dimensions of chronicity and control are the distinctive analytical issues. They lead on to consideration of patterns of sociality related to chronic conditions and their treatment...

See full abstract

Do Danes enjoy a high performing chronic care system? Hernández-Quevedo C, Tellerup MO, Juul A, Rudkjøbing A , Birk HO, Krasnik, A: Eurohealth 18(1): 26-29, 2012. 

The trends in population health in Denmark are similar to those in most Western European countries. Major health issues include, among others, the high prevalence of chronic illnesses and lifestyle related risk factors such as obesity, tobacco, physical inactivity and alcohol. This has pressed the health system towards a model of provision of care based on the management of chronic care conditions. While the Chronic Care Model was introduced in 2005, the Danish health system does not fulfil the ten key preconditions that would characterise a high performing chronic care system. As revealed in a recent report,1 the fragmented structure of the Danish health system poses challenges in providing effectively coordinated care to patients with chronic diseases.

see full text

Do immigrants from Turkey, Pakistan and Ex-Yugoslavia with newly diagnosed type 2 diabetes initiate recommended statin therapy to the same extent as Danish-born residents? A nationwide register study. Sanchez-Ramirez DC, Krasnik A, Kildemoes HW. Eur J Clin Pharmacol. 2013 Jan;69(1):87-95. 

PURPOSE: To explore whether newly diagnosed type 2 diabetes patients without previous cardiovascular disease (CVD) initiate preventive statin therapy regardless of ethnic background. METHODS: Using nationwide individual-level registers, we followed a cohort of Danish-born residents and immigrants from Turkey, Pakistan and Ex-Yugoslavia, all without previous diabetes or CVD, during the period 2000-2008 for first dispensing of oral glucose-lowering medication (GLM), first dispensing of statins and register-markers of CVD (N = 3,764,620). Logistic regression analyses were used to test whether the odds ratios (ORs) of early statin therapy initiation (within 180 days after first GLM dispensing) are the same regardless of ethnic background...

See full abstract

Integrated care: a Danish perspective. Rudkjøbing A, Tellerup MO, Birk HO, Juul A, Hernández-Quevedo C, Krasnik A: British Medical Journal 345:e4451, 2012. 

Despite three decades of reform Denmark’s health sector is still struggling to provide coordinated care for an ageing population with a high burden of chronic disease. Andreas Rudkjøbing and colleagues describe recent initiatives to improve continuity of care...

See full abstract

Is the high-risk strategy to prevent cardiovascular disease equitable? A pharmacoepidemiological cohort study. Kildemoes HW, Diderichsen F, Krasnik A, Lange T, Andersen M: BMC Public Health 12(1): 610, 2012. 

We aimed to examine whether the Danish implementation of the strategy to prevent cardiovascular disease (CVD) by initiating statin (HMG-CoA reductase inhibitor) therapy in high-risk individuals is equitable across socioeconomic groups. METHODS: Cohort study, Applying individual-level nationwide register information on socio-demographics, dispensed prescription drugs and hospital discharges, all Danish citizens aged 20+ without previous register-markers of CVD, diabetes or statin therapy were followed during 2002-2006 for first occurrence of myocardial infarction (MI) and a dispensed statin prescription (N=3.3 mill)...

see full abstract

see full text

Living by numbers. The dynamic interplay of measurement technologies, asymptomatic conditions and preventive medication among older adults in Denmark. Oxlund B. Suomen Antropologi: Journal of the Finnish Anthropological Society. 37(3), 2012.

Mindre er måske mere – Kan medicinordination til ældre mennesker forbedres? Vass M, Hendriksen C: Månedsskr Almen Prakt. 90: 953-64, 2012. 

»Less is more« hedder det inden for blues og jazz – når feeling og musikalitet skal fremmes. Måske kan det samme gælde over for vore ældre patienter – at mindre af den rette medicin kan være mere effektiv og en bedre behandling? Artiklen giver overblik over den komplicerede håndtering, når mange medikamenter skal benyttes samtidig – partituret for den almenmedicinske dirigent.

Praktiserende læger er usikre på subkutan medicinering hos terminale patienter (Low confidence among general practitioners in end-of-life care and subcutaneous administration of medicine) Gorlen T, Gorlen TF, Vass M, Neergaard MA. Ugeskrift for Laeger 174/34: 1887, 2012. 

The aim of this study was to determine if GPs used SC needle and medication in end-of-life care, if they felt confident about being principally responsible for palliative trajectories and whether such confidence was associated with GP characteristics...

see full article (in english)

Statin utilization accoding to indication and age: A Danish cohort study on changing prescribing and purchasing behaviour. Kildemoes HW, Vass M, Hendriksen C, Andersen M. Health Policy 108(2-3): 216-27, 2012. 

The aim was to describe trends in Danish statin utilization according to indication and age during 1996-2009, and to analyse changing prescribing and purchasing behaviour during time intervals (driver periods) a priori defined by potential influential factors. METHODS: A nationwide cohort (N=4,998,580) was followed in Danish individual-level registries. Based on a hierarchy of register markers of indications for statin prescribing, we analysed incidence and prevalence of use by age and indication (age≥ 40)...

see full abstract

Use of Cross-Border Healthcare Services among Ethnic Danes, Turkish Immigrants and Turkish Descendants in Denmark: a combined survey and registry study. Nielsen SS, Yazici S, Petersen SG, Blaakilde AL, Krasnik A. BMC Health Services Research 13;12(1):390, 2012. 

Our objective was to investigate use of healthcare in a foreign country in Turkish immigrants, their descendants, and ethnic Danes. METHODS: The study was based on a nationwide survey in 2007 with 372 Turkish immigrants, 496 descendants, and 1,131 ethnic Danes aged 18-66. Data were linked to registry data on socioeconomic factors. Using logistic regression models, use of doctor, specialist doctor, hospital, dentist in a foreign country as well as medicine from abroad were estimated. Analyses were adjusted for socioeconomic factors and health symptoms. RESULTS: Overall, 26.6% among Turkish immigrants made use of cross-border healthcare, followed by 19.4% among their descendants to 6.7% among ethnic Danes...

see full abstract

 Program 5 - Health Promotion and InnovationTil toppen

Careful Science? Body work and Care Practices in Clinical Trials. Jespersen AP, Bønnelycke J, Hriksen HH. Sociology of Health and Illness. Accepted, 2012.

Cultural Analysis as Intervention. Guest Editorial: Jespersen AP, Petersen MK, Ren C, Sandberg M: Science Studies 25(1): 3-12, 2012. 

Recently, cultural analyses – especially ethnographic descriptions of everydaylife practices – seem to have found new audiences situated within what Nigel Thrift has termed ‘soft capitalism’. As argued by Thrift (2006), soft capitalism (Thrift, 1997) is characterised by three features: a mobilisation of a! ective knowledge in order to create new encounters with increasingly empathetic commodities; an increased focus on co-creation, hereby bringing the consumer closer to these empathetic commodities; and the creation of new active spaces for thinking, relating, inventing and consuming...

see full text

Hvad er Det aldrende samfund?: Perspektiver fra humanistisk aldringsforskning. Otto L: Gerontologi 28(2): 17-18, 2012. 

Det aldrende samfund er ikke kun noget, der vedrører eller omhandler ældre mennesker. Det er noget, vi alle sammen, uanset alder, berøres af. Kulturelt set er der dog ikke en fælles forståelse af, hvad det betyder. I nogle sammenhænge fokuseres på de økonomiske konsekvenser af den skæve aldersfordeling i samfundet og de stigende sundhedsudgifter i forbindelse med de kroniske sygdomme, som følger med levetidsforlængelsen. I andre sammenhænge er der tegn på en spirende ny aldersforståelse, hvor aldring er andet og mere end svækkelse. Samfundsmæssigt er der en forventning om, at ældre er mere mobile, ressourcestærke, sunde og arbejdsdygtige længere end før, og mange ældre oplever heller ikke sig selv som gamle, men som aktive og uafhængige seniorer, der har ret til et godt liv. Den humanistiske aldringsforskning studerer samspillet mellem samfundets udvikling og individers selvforståelse og selvomsorg.

Making Consultations run smoothly: An analysis of Doctor’s skilful use of time inspired by science and technology studies. Jespersen AP, Elgaard Jensen T. Time & Society 21(3): 330-350, 2012. 

This article investigates the skilful use of time in general practice consultations. It argues that consultation work involves social and material interactions, which are only partially conceptualized in existing medical practice literatures. As an alternative, this article employs ideas from the field of science and technology studies (STS), including notions of relationality, multiplicity and otherness. Through this lens, and based on extensive fieldwork, it describes the daily work of arranging time before, during and after consultations. In conclusion, it suggests that a STS-inspired analysis opens up a wider discussion of time as a complex resource and problem in general practice...

see full abstract

see full text

Negotiating the Healthy Old Body: Health Promotion, Prevention, and Physical Activity, “Theorizing Age”. Otto L. special issue of The International Journal of Ageing and Later Life. In press, 2012. 

Why ‘synergy’ fails to adequately characterise interdisciplinary collaboration. Jespersen AP, Andersen MC, Bønnelycke J. STS Encounters. Accepted, 2012.