Publikationer 2015 – Københavns Universitet

Videresend til en ven Resize Print Bookmark and Share

Sund Aldring > Publikationer > Videnskabelige publikationer > Publikationer 2015

Publications 2015

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.

Theme 1Til toppen

Bødker M. The negotiation of needs, resources and potentials in an eldercare paradigm of help to self-help. European Journal of Public Health. 25(3): 352, 2015.

Ertner M. Different generalizations of the elderly in design of welfare technology. STS Encounters. Accepted, 2015.

Handlos LN, Olwig KF, Bygbjerg IC, Kristiansen M and Norredam M. Return migration among elderly, chronically ill Bosnian refugees: Does health matter? International Journal of Environmental Research and Public Health. 12(10): 12643-61, 2015.

Abstract:

Elderly migrants constitute a considerable share of global return migration; nevertheless, literature on the health aspects of the return migration among these migrants is still scarce. This study explores the significance of return migration among elderly, chronically ill Bosnian refugees from Denmark and the role of health issues in their decision to return. It is based on semi-structured interviews with 33 elderly, chronically ill Bosnian refugees who have moved back to Bosnia and Herzegovina, and 10 elderly, chronically ill Bosnian refugees who have remained in Denmark.

See full abstract

Holm L, Jespersen AP, Nielsen DS, Frøst MB, Reitelseder S, Jensen T, Engelsen SB and Kjær M. Hurrah for the increasing longevity: feasible strategies to counteract age-related loss of skeletal muscle mass. Scandinavian Journal of Medicine & Science in Sports. 25(1), 2015.

Jensen T. The importance of age perceptions and nutritional science to early 20th century institutional diets. Social History of Medicine. Accepted, 2015.

Kriegbaum M, Hendriksen C, Vass M, Mortensen EL and Osler M. Hypnotics and mortality – partial confounding by disease, substance abuse and socioeconomic factors? Pharmacoepidemiology & Drug Safety. 24(7): 779-83, 2015.


Abstract

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

See full abstract

Kristiansen M, Lue-Kessing L, Norredam M, Krasnik A. Migrants’ perceptions of aging in Denmark and attitudes towards remigration: findings from a qualitative study. BMC Health Services Research. 15: 225, 2015.


Abstract

The increasing number of elderly migrants in Europe poses challenges for the organisation of healthcare and social services if these migrants do not remigrate to their countries of birth at old age. More insight into perceptions of aging among migrant women is needed to inform service delivery for culturally and linguistic diverse populations, yet few studies have explored this field. The aim of this study is to explore perceptions of aging among middle-aged migrant women, with emphasis on identifying factors shaping their decisions on whether to remigrate or stay in Denmark during old age. The study is based on 14 semi-structured interviews including a total of 29 migrant women residing in Copenhagen, Denmark. The women were born in Somalia, Turkey, India, Iran, Pakistan, or Middle Eastern countries. The majority of participants were middle-aged and had one or more chronic illnesses. The analysis was inspired by phenomenological methods and guided by theory on access to services, social relations, and belonging.

See full abstract

Lassen AJ and Jespersen AP. Ældres hverdagspraksisser i aldringspolitikken: Om synkroniseringsarbejdet imellem hverdag og politik (Old People’s Everyday Practices and Ageing Policy – On the Synchronisation between Everyday Life and Policy). Kulturstudier. 1: 79-99, 2015.

Lassen AJ. Biopolíticas de la vejez – Cómo el conocimiento sobre el envejecimiento forma políticas de envejecimiento activo. Sociología Histórica. Accepted, 2015.

 

Michaelis C, Kristiansen, M and Norredam M. Quality of life and coping strategies among immigrant women living with pain in Denmark: a qualitative study. BMJ Open. 5(7):e008075, 2015.

Abstract:

To examine quality of life and coping strategies among immigrant women living with chronic pain. Qualitative content analysis based on in-depth semi-structured interviews. A clinic specifically targeting immigrants at a larger university hospital in Copenhagen,Denmark. Non-western female immigrant patients suffering from chronic pain (n=13). Experiences of the impact of chronic pain on quality of life.

See full abstract

Ludvigsen B. Market thinking and home nursing. Perspectives on new socialities in health care in Denmark. Medical Anthropology at Home: New Socialities. Accepted, 2015.

Ludvigsen B. Ældre mennesker, medicin og sociale relationer: Perspektiver på primær sundhedstjeneste – møder mellem mennesker (Older people, medicine and social relations: Perspectives on primary health service – encounters between people). Nyt Nordisk Forlag Arnold Busck / Schønberg. Accepted, 2015.

Ludvigsen B. Når ældre mennesker bliver gamle. Betydningen af velfærdsstaten og medborgerskabet (When older people are getting old. The importance of the welfare state and citizenship). Tidsskrift for Antropologi. Accepted, 2015.

Mikkelsen HH. “Vi fandt ungdom i seniorboliger”: Aldring, autonomi og kollektiv historiefortælling historiefortælling (”We found youth in senior housing”: Aging, autonomy and collective historical narration). Gerontologi. 2: 26-31, 2015.

Mikkelsen HH. The Invasion of Solitude: Successful aging in Denmark through the Lacanian Real. Ethos. Accepted, 2015.

Nørtoft KPJ. Uafhængighed og identitet i det sene hverdagsliv – Gerdas historie (Independence and identity in late everyday life – Gerda’s story). Gerontologi, Accepted, 2015.

Rudkjøbing A, Vrangbaek K, Birk HO, Andersen JS and Krasnik A. Evaluation of a policy to strengthen case management and quality of diabetes care in general practice in Denmark. Health Policy. 119(8): 1023-30, 2015.

Abstract

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

See full abstract

Book chapters:

Christensen LT. Selvhjulpne borgere. Bag om fænomenet hverdagsrehabilitering (Self-reliant Citizens. Behind the phenomenon everyday rehabilitation).  In: Oxlund B (ed.): Aldringens Veje. Sundhed og socialitet i danske livsforløb. Frydenlund. Accepted, 2015.

Lassen AJ and Jespersen AP. Getting old and keeping going: The motivation techniques of active ageing in Denmark. In: Lamb S (ed.): Successful aging? Global perspectives on a contemporary obsession. Rutgers University Press. Accepted, 2015.

Lassen AJ. Aktiv aldring imellem hverdag og policy: En etnologisk analyse af hvordan aktiv aldring former det gode ældreliv (Active aging between everyday life and policy: An ethnological analysis of how active aging forms the good senior life). In: Oxlund B (ed.) Aldringens veje. Frydenlund. Accepted, 2015.

Lassen AJ. Forming old age: Innovation partnerships, activity centers and billiards tables as active ageing technologies. In: Majerus B. (ed.) Framing age: Contested knowledge in science and politics. Routledge. Accepted, 2015.

Ludvigsen B. At være bundet til sit hjem (To be tied to your home). Aldringens veje: Sundhed og socialitet i danske livsforløb. In: Oxlund B (ed.) Frydenlund. Accepted, 2015.

Mikkelsen HH. “Ingen undskyldninger”: Ensomhed og succesfuld aldring (”No excuses”: Loneliness and succesful aging. In: Oxlund B (ed.) Frydenlund. Accepted, 2015.

Theme 2Til toppen

Ayata C and Lauritzen M. Spreading Depression, Spreading Depolarizations, and the Cerebral Vasculature. Physiological Review. 95: 953-93, 2015.

Abstract

Spreading depression (SD) is a transient wave of near-complete neuronal and glial depolarization associated with massive transmembrane ionic and water shifts. It is evolutionarily conserved in the central nervous systems of a wide variety of species from locust to human. The depolarization spreads slowly at a rate of only millimeters per minute by way of grey matter contiguity, irrespective of functional or vascular divisions, and lasts up to a minute in otherwise normal tissue. As such, SD is a radically different breed of electrophysiological activity compared with everyday neural activity, such as action potentials and synaptic transmission.

See full abstract

Bach B, Lee C, Mortensen EL and Simonsen E. How Do DSM-5 Personality Traits Align With Schema Therapy Constructs? Journal of Personality Disorders. 25:1-28, 2015.

Abstract

DSM-5 offers an alternative model of personality pathology that includes 25 traits. Although personality disorders are mostly treated with psychotherapy, the correspondence between DSM-5traits and concepts in evidence-based psychotherapy has not yet been evaluated adequately. Suitably, schema therapy was developed for treating personality disorders, and it has achieved promising evidence. The authors examined associations between DSM-5 traits and schematherapy constructs in a mixed sample of 662 adults, including 312 clinical participants. 

See full abstract

Baranowski M, Blachnio-Zabielska AU, Charmas M, Helge JW, Dela F, Ksiazek M, Dlugolecka B, Klusiewicz A, Chabowski A and Gorski J. Exercise increases sphingoid base-1-phosphate levels in human blood and skeletal muscle in a time- and intensity-dependent manner. European Journal of Applied Physiology. 115: 993-1003, 2015.

Abstract

Sphingosine-1-phosphate (S1P) regulates cardiovascular function and plays an important role in muscle biology. We have previously reported that cycling exercise increased plasma S1P. Here, we investigated the effect of exercise duration and intensity on plasma and skeletal muscle S1P levels. In the first experiment, 13 male athletes performed a 60-min exercise at 65 % of VO2max and a graded exercise until exhaustion on a rowing ergometer. Samples of the venous blood were taken, and plasma, erythrocytes and platelets were isolated. In the second experiment, ten male moderately active subjects performed three consecutive periods of one-leg knee extension exercise (at 25, 55 and 85 % of the maximal workload). Muscle biopsies and blood samples from the radial artery and femoral veins were taken.

See full abstract

Beyer R, Kongsgaard M, Kjaer BH, Ohlenschlaeger T, Kjaer M and Magnusson SP. Heavy slow resistance versus eccentric training as a treatment of Achilles tendinopathy: A randomized controlled trial. American Journal of Sports Medicine. 43: 1704-11, 2015.

Abstract

Previous studies have shown that eccentric training has a positive effect on Achilles tendinopathy, but few randomized controlled trials have compared it with other loading-based treatment regimens. To evaluate the effectiveness of eccentric training (ECC) and heavy slow resistance training (HSR) among patients with midportion Achilles tendinopathy. Randomized controlled trial; Level of evidence, 1. A total of 58 patients with chronic (>3 months) midportion Achilles tendinopathy were randomized to ECC or HSR for 12 weeks. Function and symptoms (Victorian Institute of Sports Assessment-Achilles), tendon pain during activity (visual analog scale), tendon swelling, tendon neovascularization, and treatment satisfaction were assessed at 0 and 12 weeks and at the 52-week follow-up. Analyses were performed on an intention-to-treat basis.

See full abstract

Bo S, Bach B, Mortensen EL and Simonsen E. Reliability and Hierarchical Structure of DSM-5 Pathological Traits in a Danish Mixed Sample. Journal of Personality Disorders. 23:1-18, 2015. 

Abstract

In this study we assessed the DSM-5 trait model in a large Danish sample (n = 1,119) with respect to reliability of the applied Danish version of the Personality Inventory for DSM-5 (PID-5) self-report form by means of internal consistency and item discrimination. In addition, we tested whether the five-factor structure of the DSM-5 trait model can be replicated in a Danish independent sample using the PID-5 self-report form. Finally, we examined the hierarchical structure of DSM-5 traits. 

See full abstract

Boushel R, González-Alonso J, Calbet JAL, Helge JW, Søndergaard H, Munch-Andersen Th, van Hall G and Calbet JL. Maintained peak leg and pulmonary VO2 despite substantial reduction in muscle mitochondrial capacity. Scandinavian Journal of Medicine & Science in Sports. 25(4): 135-143. Accepted, 2015.

Abstract

We recently reported the circulatory and muscle oxidative capacities of the arm after prolonged low-intensity skiing in the arctic (Boushel et al., 2014). In the present study, leg VO2 was measured by the Fick method during leg cycling while muscle mitochondrial capacity was examined on a biopsy of the vastus lateralis in healthy volunteers (7 male, 2 female) before and after 42 days of skiing at 60% HR max. Peak pulmonary VO2 (3.52 ± 0.18 L.min(-1) pre vs 3.52 ± 0.19 post) and VO2across the leg (2.8 ± 0.4L.min(-1) pre vs 3.0 ± 0.2 post) were unchanged after the ski journey. Peakleg O2 delivery (3.6 ± 0.2 L.min(-1) pre vs 3.8 ± 0.4 post), O2 extraction (82 ± 1% pre vs 83 ± 1 post), and muscle capillaries per mm(2) (576 ± 17 pre vs 612 ± 28 post) were also unchanged; however, leg muscle mitochondrial OXPHOS capacity was reduced (90 ± 3 pmol.sec(-1) .mg(-1) pre vs 70 ± 2 post, P < 0.05) as was citrate synthase activity (40 ± 3 μmol.min(-1) .g(-1) pre vs 34 ± 3 vs P < 0.05). 

See full abstract

Bruun Christiansen L, Prats C, Hyttel P and Koch J. Ultra structural myocardial changes in seven cats with spontaneous hypertrophic cardiomyopathy. Journal of Veterinary Cardiology. Accepted, 2015. 

Abstract

Hypertrophic cardiomyopathy (HCM) is the most common heart disease in cats and shares clinical and pathological characteristics with human HCM. Little is known about the pathogenic mechanisms underlying development of spontaneous feline HCM. The study population consisted of seven cats diagnosed with HCM and eight age-matched cats with no evidence of cardiac disease. Fresh myocardial biopsies taken from the middle of the left ventricular posterior free wall were obtained and examined with transmission electron microscopy.

Buhmann CB, Nordentoft M, Ekstroem M, Carlsson J and Mortensen EL. The effect of flexible cognitive behavioral therapy and medical treatment, including antidepressants on PTSD and depression in traumatized refugees - a randomized controlled clinical trial. British Journal of Psychiatry. Accepted, 2015. 

Buhmann C, Andersen I,  Mortensen EL, Ryberg J, Nordentoft M and Ekstroem M. Cognitive Behavioral Psychotherapeutic treatment at a psychiatric trauma clinic for Refugees: description and evaluation. Torture. 25: 17-32, 2015. 

Abstract

Cognitive behavioural therapy (CBT) with trauma focus is the most evidence supported psychotherapeutic treatment of PTSD, but few CBT treatments for traumatized refugees have been described in detail. To describe and evaluate a manualized cognitive behavioral therapy for traumatized refugees incorporating exposure therapy, mindfulness and acceptance and commitment therapy. 85 patients received six months' treatment at a Copenhagen Trauma Clinic for Refugees and completed self-ratings before and after treatment. The treatment administered to each patient was monitored in detail. The changes in mental state and the treatment components associated with change in state were analyzed statistically.

See full abstract

Buhmann C,  Mortensen EL, Nordentoft M, Ryberg J and Ekstroem M. Follow-up study of the treatment outcomes at a psychiatric trauma clinic for refugees. Torture. 25: 1-16, 2015.

Abstract

To describe change in mental health after treatment with antidepressants and trauma-focused cognitive behavioral therapy. Patients receiving treatment at the Psychiatric Trauma Clinic for Refugees in Copenhagen completed self-ratings of level of functioning, quality of life, and symptoms of PTSD, depression and anxiety before and after treatment. Changes in mental state and predictors of change were evaluated in a sample that all received well-described and comparable treatment.

See full abstract

Calbet JAL, González-Alonso J, Helge JW, Søndergaard H, Munch-Andersen Th, Saltin B and Boushel R. Central and peripheral hemodynamics in exercising humans: leg vs arm exercise. Scandinavian Journal of Medicine & Science in Sports. 25(4): 144-157. Accepted, 2015.

Abstract

In humans, arm exercise is known to elicit larger increases in arterial blood pressure (BP) than leg exercise. However, the precise regulation of regional vascular conductances (VC) for the distribution of cardiac output with exercise intensity remains unknown. Hemodynamic responses were assessed during incremental upright arm cranking (AC) and leg pedalling (LP) to exhaustion (Wmax ) in nine males. Systemic VC, peak cardiac output (Qpeak ) (indocyanine green) and stroke volume (SV) were 18%, 23%, and 20% lower during AC than LP. The mean BP, the rate-pressure product and the associated myocardial oxygen demand were 22%, 12%, and 14% higher, respectively, during maximal AC than LP. Trunk VC was reduced to similar values at Wmax . 

See full abstract

Christensen GT, Molbo D, Angquist LH, Mortensen EL, Christensen K, Sørensen TIA and Osler M. Cohort Profile: The Danish Conscription Database (DCD): A cohort of 728 160 men born from 1939 through 1959. International Journal of Epidemiology. 44: 423-440, 2015.

Abstract

The Danish Conscription Database (DCD) was established to enable studies of the influence of early physical and mental exposures on adverse health and social outcomes from a life-course perspective. In Denmark, all young men are requested to appear before the conscription board when they turn 18 years, to be assessed for military service. The DCD was established by digitizing information from conscription board register cards on the height, weight, educational level, intelligence test score and examination details of Danish conscripts. The DCD contains information on 728,160 men born from 1939 through 1959 and examined by the conscription board from 1957 through 1984. The unique Danish personal identification number of each individual conscript has been traced, and this allows linkage of the DCD to all Danish health and socioeconomic registers. 

See full abstract

Christensen J, Fisker A, Mortensen EL, Olsen LR, Mortensen OS, Hartvigsen J and Langberg H. Comparison of mental distress in patients with low back pain and a population-based control group measured by Symptoms Check List - A case-referent study. Scandinavian Journal of Public Health. 43: 638-647, 2015.

Abstract

Mental distress is common in persons experiencing low back pain and who are sick-listed or at risk of being sick-listed. It is, however, not known how mental distress measured by the Symptoms Check List-90 differs between patients with low back pain and the general population. The objective of this study was to compare mental symptoms and distress as measured by the Symptoms Check List-90 in sick-listed or at risk of being sick-listed patients with low back pain with a population-based control group. Mental distress was compared in a group of patients with low back pain (n=770) and a randomly selected population-based reference group (n=909). Established Danish cut-off values formental distress were used to evaluate the mental distress status in the low back pain and control group and logistic regression was used to calculate odds ratios for the Global Severity Index and the symptom scales of the Symptoms Check List-90 while controlling for baseline demographic differences between the groups.

See full abstract

Christensen JA, Carrillo O, Leary EB, Peppard PE, Young T, Sorensen HB, Jennum P and Mignot E. Sleep-stage transitions during polysomnographic recordings as diagnostic features of type 1 narcolepsy. Sleep Medicine. 16: 1558-66, 2015.

Abstract

Type 1 narcolepsy/hypocretin deficiency is characterized by excessive daytime sleepiness, sleep fragmentation, and cataplexy. Short rapid eye movement (REM) latency (≤15 min) during nocturnal polysomnography (PSG) or during naps of the multiple sleep latency test (MSLT) defines a sleep-onset REM sleep period (SOREMP), a diagnostic hallmark. We hypothesized that abnormal sleep transitions other than SOREMPs can be identified in type 1narcolepsy. Sleep-stage transitions (one to 10 epochs to one to five epochs of any other stage) and bout length features (one to 10 epochs) were extracted from PSGs. The first 15 min of sleep were excluded when a nocturnal SOREMP was recorded. F0.1 measures and receiver operating characteristic curves were used to identify specific (≥98%) features. A data set of 136 patients and 510 sex- and age-matched controls was used for the training. A data set of 19 cases and 708 sleep-clinic patients was used for the validation.

See full abstract

Christensen JA, Munk EG, Peppard PE, Young T, Mignot E, Sorensen HB and Jennum P. The diagnostic value of power spectra analysis of the sleep electroencephalography in narcoleptic patients. Sleep Medicine. 16: 1516-27, 2015.

Abstract

Manifestations of narcolepsy with cataplexy (NC) include disturbed nocturnal sleep - hereunder sleep-wake instability, decreased latency to rapid eye movement (REM) sleep, and dissociated REM sleep events. In this study, we characterized the electroencephalography (EEG) of various sleep stages in NC versus controls. EEG power spectral density (PSD) was computed in 136 NC patients and 510 sex- and age-matched controls. Features reflecting differences in PSD curves were computed. A Lasso-regularized regression model was used to find an optimal feature subset, which was validated on 19 NC patients and 708 non-NC patients from a sleep clinic. Reproducible features were analyzed using receiver operating characteristic (ROC) curves.

See full abstract

Christiansen LB, Dela F, Koch J, Hansen CN, Leifsson PS and Yokota T. Impaired cardiac mitochondrial oxidative phosphorylation and enhanced mitochondrial oxidative stress in feline hypertrophic cardiomyopathy. American Journal of Physiology: Heart and Circulatory Physiology. 308: H1237-H1247, 2015.

Abstract

Mitochondrial dysfunction and oxidative stress are important players in the development of various cardiovascular diseases, but their roles in hypertrophic cardiomyopathy (HCM) remain unknown. We examined whether mitochondrial oxidative phosphorylation (OXPHOS) capacity was impaired with enhanced mitochondrial oxidative stress in HCM. Cardiac and skeletal muscles were obtained from 9 domestic cats with spontaneously occurring HCM with preserved left ventricular systolic function and from 15 age-matched control cats. Mitochondrial OXPHOS capacities with non-fatty acid and fatty acid substrates in permeabilized fibers and isolated mitochondria were assessed using high-resolution respirometry. ROS release originating from isolated mitochondria was assessed by spectrofluorometry.

See full abstract

Christiansen LB, Dela F, Koch J and Yokota T. Tissue-specific and substrate-specific mitochondrial bioenergetics in feline cardiac and skeletal muscles. Journal of Veterinary Medical Science. 77: 669-675, 2015.

Abstract

No studies have investigated the mitochondrial function in permeabilized muscle fiber from cats. The aim of this study was to investigate tissue-specific and substrate-specific characteristics ofmitochondrial oxidative phosphorylation (OXPHOS) capacity in feline permeabilized oxidative muscle fibers. Biopsies of left ventricular cardiac muscle and soleus muscle, a type I-rich oxidative skeletal muscle, were obtained from 15 healthy domestic cats. Enzymatic activity of citrate synthase (CS), a biomarker of mitochondrial content, was measured. Mitochondrial OXPHOS capacity with various kinds of non-fatty-acid substrates and fatty-acid substrate in permeabilized muscle fiber was measured by using high-resolution respirometry. 

See full abstract

Clark AJ, Salo P, Lange T, Jennum P, Virtanen M, Pentti J, Kivimäki M, Vahtera J and Rod NH. Onset of impaired sleep as a predictor of change in health-related behaviours; analysing observational data as a series of non-randomized pseudo-trials. International Journal of Epidemiology. 44: 1027-37, 2015.

Abstract

Changes in health-related behaviour may be a key mechanism linking impaired sleep to poor health, but evidence on this is limited. In this study, we analysed observational data to determine whether onset of impaired sleep is followed by changes in health-related behaviours. We used data from 37,508 adults from the longitudinal Finnish Public Sector Study. In analysis of 59 152 person-observations on duration and quality of sleep and health-related behaviours (alcohol consumption, smoking, physical activity and weight control), data were treated as a series of non-randomized pseudo-trials with strict predefined criteria for data inclusion and temporality.

See full abstract

Couppe C, Svensson RB, Kongsgaard M, Kovanen V, Grosset JF, Snorgaard O, Bencke J, Larsen JO, Bandholm T, Christensen TM, Boesen AP, Helmark IC, Aagaard P, Kjaer M and Magnusson SP. Human Achilles tendon glycation and function in diabetes. Journal of Applied Physiology. Accepted, 2015.

Abstract

Diabetic patients have an increased risk of foot ulcers, and glycation of collagen may increase tissue stiffness. We hypothesized that the level of glycemic control (glycation) may affect Achilles tendon stiffness, which can influence gait pattern. We therefore investigated the relationship between collagen glycation, Achilles tendon stiffness parameters, and plantar pressure in poorly (n = 22) and well (n = 22) controlled diabetic patients, including healthy age-matched (45-70 yr) controls (n = 11). There were no differences in any of the outcome parameters (collagen cross-linking or tendon stiffness) between patients with well-controlled and poorly controlled diabetes. The overall effect of diabetes was explored by collapsing the diabetes groups (DB) compared with the controls. 

See full abstract

Dahl R, Larsen S, Dohlmann TL, Qvortrup K, Helge JW, Dela F and Prats C. Three dimensional reconstruction of the human skeletal muscle mitochondrial network as a tool to assess mitochondrial content and structural organization.  Acta Physiology.  213: 145-55, 2015.

Abstract

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

See full abstract

Dall CH, Gustafsson F, Christensen SB, Dela F, Langberg H and Prescott E. Effect of moderate- versus high-intensity exercise on vascular function, biomarkers and quality of life in heart transplant recipients: A randomized, crossover trial. Journal of Heart and Lung Transplantation. 34: 1033-1041, 2015.

Abstract

Growing evidence in long-term treatment of heart transplant (HTx) recipients indicates effects of high-intensity interval training (HIIT) on several parameters, including oxygen uptake, vascular function and psychological distress. In this study we compare the effect of HIIT vs continued moderate training (CON) on vascular function, biomarkers and health-related quality oflife (HRQoL) in HTx recipients. A randomized, controlled crossover trial of stable HTx recipients >12 months after transplantation was done on patients with 12 weeks of HIIT or 12 weeks of CON, followed by a 5-month washout and crossover. Outcomes included endothelial function, arterial stiffness,biomarkers, HRQoL and markers of anxiety and depression.

See full abstract

Dich N, Hansen ÅM, Avlund K, Lund R,  Mortensen EL, Bruunsgaard H and Rod NH. Early Life Adversity Potentiates the Effects of Later Life Stress on Cumulative Physiological Dysregulation. Anxiety, Stress & Coping. 28: 372-390, 2015.

Abstract

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

See full abstract

Dela F. Functional adaptation of the human beta-cells after frequent exposure to noradrenaline. Journal of Physiology. 593: 3199-3206, 2015.

Abstract

Physical training decreases glucose- and arginine-stimulated insulin secretion. The mechanism by which the pancreatic β-cells adapt to the training status of the individual is not known. We hypothesized that the adaptation is mediated via the frequent exercise-induced increases in sympathetic activity. Simulation of exercise-induced increases in plasma noradrenaline (NA) concentrations was carried out in nine untrained men (age: 25 ± 1 years (mean ± SEM); BMI: 24 ± 1 kg m(-2) ), who received infusions of NA (0.2 μg kg(-1) min(-1) ) for 45 min every day for 10 days. The insulin response to glucose was measured during hyperglycaemic (20 mmol l(-1) ) clamps before and after the NA infusion period. During NA infusions mean arterial blood pressure increased (from 89 ± 2 to 110 ± 5 mmHg, P < 0.05) and heart rate decreased (from 78 ± 7 to 69 ± 12 beats min(-1) , P < 0.05).

See full abstract

Dela F.  Mitochondrial Physiology - from organelle to organism. Acta Scandinavica Physiologica. 213: 752, 2015.

Dela F and Helge JW. Comment on “Brown Adipose Tissue Improves Whole-Body Glucose Homeostasis and Insulin Sensitivity in Humans”. Letter. Diabetes. 64(6): e12 - 13, 2015.

See ful abstract

Desler C, Frederiksen JH, Angleys M, Maynard S, Keijzers G, Fagerlund B, Mortensen EL, Osler M, Lauritzen M, Bohr VA and Rasmussen LJ. Increased deoxythymidine triphosphate levels is a feature of relative cognitive decline. Mitochondrion. 25: 34-7, 2015.

Abstract

Mitochondrial bioenergetics, mitochondrial reactive oxygen species (ROS) and cellular levels of nucleotides have been hypothesized as early indicators of Alzheimer's disease (AD). Utilizingrelative decline of cognitive ability as a predictor of AD risk, we evaluated the correlation between change of cognitive ability and mitochondrial bioenergetics, ROS and cellular levels of deoxyribonucleotides. Change of cognitive abilities, scored at ages of approximately 20 and 57 was determined for a cohort of 1985 male participants. Mitochondrial bioenergetics, mitochondrial ROS and whole-cell levels of deoxyribonucleotide triphosphates were measured in peripheral blood mononuclear cells (PBMCs) from a total of 103 selected participants displaying the most pronounced relative cognitive decline and relative cognitive improvement.

See full abstract

Elkjaer H, Kristensen E, Mortensen EL and Poulsen S. Efficacy of specialized incest group psychophearpy in reducing symptoms of PTS: 5 year follow-up of a randomized trial. European Psychiatry. Accepted, 2015.

Eriksen HF, Kesmodel US, Pedersen LH and Mortensen,EL. No assoctiation between prenatal exposure to psychotrophics and intelligence age five. Acta Obstetricia et Gynecologica Scandinavica. 94: 501-507, 2015.

Abstract

To examine associations between prenatal exposure to selective serotonin reuptake inhibitors (SSRIs)/anxiolytics and intelligence assessed with a standard clinical intelligence test atage 5 years. Longitudinal follow-up study. Denmark, 2003-2008. A total of 1780 women and their children sampled from the Danish National Birth Cohort. Self-reported information on use of SSRI and anxiolytics was obtained from the Danish National Birth Cohort at the time of consent and from two prenatal interviews. Intelligence was assessed at age 5 years, and parental education, maternal intelligence quotient (IQ), maternal smoking and alcohol consumption in pregnancy, the child's age at testing, sex, and tester were included in the full model. The IQ of 13 medication-exposed children was compared with the IQ of 19 children whose mothers had untreated depression and 1748 control children.

See full abstract

Eriksen L, Grønbæk M, Helge JW and Tolstrup JS. Cardiorespiratory fitness reference for Danish adults - and the association with physical activity and sitting time. Scandinavian Journal of Medicine & Science in Sports. Accepted, 2015.

Abstract

Our aim was to provide up-to-date cardiorespiratory fitness reference data for adults of all ages and to investigate associations between cardiores-piratory fitness and leisure time physical activity as well as sitting time. In the Danish Health Examination Survey 2007-2008, cardiorespiratory fitnesswas estimated in 16 025 individuals aged 18-91 years from validated cycle ergometer exercise tests. Level of leisure time physical activity (sedentary, light, moderate, and vigorous) and dailysitting time in hours was obtained from a self-administered questionnaire. Men had 20-33% highercardiorespiratory fitness than women, depending on age, and cardiorespiratory fitness decreased by 0.26 and 0.23 mL/min/kg per year in men and women, respectively. 

See full abstract

Faerch LH, Thorsteinsson B, Tarnow L, Juul HJ, Kjaer T, Kanters J, Larroude C, Dela F, Pedersen-Bjergaard U. Effects of angiotensin II receptor blockade on cerebral, cardiovascular, counter-regulatory, and symptomatic responses during hypoglycaemia in patients with type 1  Journal of the Renin-Angiotensin-Aldosterone System. Accepted, 2015. 

Abstract

High spontaneous activity of the renin-angiotensin system (RAS) results in more pronounced cognitive impairment and more prolonged QTc interval during hypoglycaemia in type 1diabetes. We tested whether angiotensin II receptor blockade improves cerebral and cardiovascularfunction during hypoglycaemia. Nine patients with type 1 diabetes and high spontaneous RAS activity were included in a double-blind, randomised, cross-over study on the effect of angiotensin II receptor antagonist (candesartan 32 mg) or placebo for one week on cognitive function, cardiovascular parameters, hormonal counter-regulatory response, substrate mobilisation, and symptoms duringhypoglycaemia induced by two hyperinsulinaemic, hypoglycaemic clamps.

See full abstract

Flensborg-Madsen T and Mortensen EL. Infant developmental milestones and adult intelligence: A 34-year follow-up. Early Human Development. 91: 393-400, 2015. 

Abstract

A number of studies suggest a positive association between faster infant motor development and intellectual function in childhood and adolescence. However, studies investigating the relationship between infant motor development and intelligence in adulthood are lacking. To investigate whether age at achievement of 12 motor developmental milestones was associated with adult intelligence and to evaluate the influence of sex, parental social status, parity, mother's cigarette consumption in the last trimester, gestational age, birthweight, and birth length on this association. Mothers of 9125 children of the Copenhagen Perinatal Cohort recorded 12developmental milestones during the child's first year of life. A subsample of the cohort comprising 1155 individuals participated in a follow-up when they were aged 20-34 years and were administered the Wechsler Adult Intelligence Scale (WAIS). Associations between motor developmentalmilestones and IQ were analysed by multiple linear regression adjusting for potential confounding factors.

See full abstract

Fløe A, Hilberg O, Wejse C, Løkke A, Ibsen R, Kjellberg J and Jennum P. The economic burden of tuberculosis in Denmark 1998-2010. Cost analysis in patients and their spouses. International journal of infectious diseases. 32:183-90, 2015.

Abstract

To evaluate the economic burden of tuberculosis (TB) in Denmark, 8,433 Danish TB-patients (1998-2010) were matched with 33,707 controls by age, gender, civil status and geography. Health-related costs (health system contacts and -procedures, medications) and socio-economic parameters (foregone earnings and social transfer expenses) were calculated on data from national databases. The same information was obtained for 3,485spouses of TB-patients, and 17,403 controls.Health-related costs were higher for cases throughout the period. Before diagnosis, cases posed € 1,180 more health costs per year than controls. Excess health costs in the 2 years around diagnosing and treating TB were € 10,509. Cases received an average excess public transfer income of € 3,345 before vs. € 3,121 after diagnosis. Average employment income deficiency was € 11,635 before vs. € 13,885 after diagnosis, but the increasing difference showed a linear shape throughout the period. Spouses also had lower income, more social transfer, and posed higher health-related costs than matched controls.

See full abstract

Gidaya N, Lee B, Burstyn I, Michael Y, Newschaffer C and Mortensen EL. In utero Exposure to β-2-adrenergic Receptor Agonist Drugs and Risk for Autism Spectrum Disorders. Pediatrics. Accepted, 2015.

Abstract

The purpose of this study was to investigate associations between use of β-2-adrenergic receptor (B2AR) agonist drugs during pregnancy and risk for autism spectrum disorders(ASD). A case-control study was conducted by using Denmark's health and population registers. Among children born between 1997 and 2006, 5200 cases with ASD admission diagnoses and 52 000 controls without ASD were identified and individually matched on month and year of birth. Conditional logistic regression models were used to estimate odds ratios (OR) and confidence intervals (CI) for any B2AR agonist exposure during pregnancy, preconception, and by trimester.

See full abstract

Gifford JR, Trinity JD, Layec G, Garten RS, Park SY, Rossman MJ, Larsen S, Dela F and Richardson RS. Quadriceps Exercise Intolerance in Patients with Chronic Obstructive Pulmonary Disease: The Role of Altered Skeletal Muscle Mitochondrial Respiration. Journal of Applied Physiology. 119: 882-888, 2015.

Abstract

This study sought to determine if qualitative alterations in skeletal muscle mitochondrial respiration, associated with decreased mitochondrial efficiency, contribute to exercise intolerance in patientswith chronic obstructive pulmonary disease (COPD). Using permeabilized muscle fibers from the vastus lateralis of 13 patients with COPD and 12 healthy controls, complex I (CI) and complex II (CII)-driven State 3 mitochondrial respiration were measured separately (State 3:CI and State 3:CII) and in combination (State 3:CI+CII). State 2 respiration was also measured. Exercise tolerance was assessed by knee extensor exercise (KE) time to fatigue. Per milligram of muscle, State 3:CI+CII and State 3:CI were reduced in COPD (P < 0.05), while State 3:CII and State 2 were not different between groups. 

See full abstract

Van Ginkel S, Amami M, Dela F, Niederseer D, Narici MV, Niebauer J, Scheiber P, Muller E and Fluck M. Adjustments of muscle capillarity but not mitochondrial protein with skiing in the elderly. Scandinavian Journal of Medicine & Science in Sports. 25: e360-367, 2015.

Abstract

Downhill skiing in the elderly increases maximal oxygen uptake (VO2max) and carbohydrate handling, and produces muscle hypertrophy. We hypothesized that adjustments of the cellular components of aerobic glucose combustion in knee extensor muscle, and cardiovascularadjustments, would increase in proportion to VO2max. Nineteen healthy elderly subjects (age 67.5 ± 2.9 years) who completed 28.5 days of guided downhill skiing over 3 months were assessed for anthropometric variables, cardiovascular parameters (heart rate, hematocrit), VO2max, and compared with controls (n = 20). Biopsies of vastus lateralis muscle were analyzed for capillary density and expression of respiratory chain markers (NDUFA9, SDHA, UQCRC1, ATP5A1) and the glucose transporter GLUT4.

See full abstract

Gnaiger E, Boushel R, Søndergaard H, Munch-Andersen Th, Damsgaard R, Hagen C, Díez-Sánchez C, Ara I, Wright-Paradis C, Schrauwen P, Hesselink M, Calbet J, Christiansen M, Helge JW and Saltin B. Preserved Mitochondrial Coupling and Adaptive Substrate Control in Skeletal Muscle of Inuit and Caucasians in the Arctic Winter. Scandinavian Journal of Medicine & Science in Sports. 25(4): 126-134. Accepted, 2015.

Abstract

During evolution, mitochondrial DNA haplogroups of arctic populations may have been selected for lower coupling of mitochondrial respiration to ATP production in favour of higher heat production. We show that mitochondrial coupling in skeletal muscle of traditional and westernized Inuit habituating northern Greenland is identical to Danes of western Europe haplogroups. Biochemical coupling efficiency was preserved across variations in diet, muscle fiber type, and uncoupling protein-3 content. Mitochondrial phenotype displayed plasticity in relation to lifestyle and environment. Untrained Inuit and Danes had identical capacities to oxidize fat substrate in arm muscle, which increased in Danes during the 42 days of acclimation to exercise, approaching the higher level of the Inuit hunters.

See full abstract

González-Alonso J, Calbet JAL, Boushel R, Helge JW, Søndergaard H, Munch-Andersen Th,  van Hall G, Mortensen SP, Secher NH and Saltin B. Blood temperature and regulation of perfusion in exercising and non-exercising human limbs. Experimental. Physiology. 100: 1118-1131, 2015.

Abstract

What is the central question of this study? Temperature-sensitive mechanisms are thought to contribute to blood-flow regulation, but the relationship between exercising and non-exercising limb perfusion and blood temperature is not established. What is the main finding and its importance? The close coupling among perfusion, blood temperature and aerobic metabolism inexercising and non-exercising extremities across different exercise modalities and activity levels and the tight association between limb vasodilatation and increases in plasma ATP suggest that both temperature- and metabolism-sensitive mechanisms are important for the control of humanlimb perfusion, possibly by activating ATP release from the erythrocytes. Temperature-sensitive mechanisms may contribute to blood-flow regulation, but the influence of temperature on perfusionto exercising and non-exercising human limbs is not established. Blood temperature (TB ), bloodflow and oxygen uptake (V̇O2) in the legs and arms were measured in 16 healthy humans during 90 min of leg and arm exercise and during exhaustive incremental leg or arm exercise.

See full abstract

Gram M, Vigelso A, Yokota T, Helge JW, Dela F and Hey-Mogensen M. Skeletal muscle mitochondrial H2O2 emission increases with immobilization and decreases after aerobic training in young and older men. Journal of Physiology. 593: 4011-4027, 2015.

Abstract

Currently, it is not known whether impaired mitochondrial function contributes to human ageing or whether potential impairments in mitochondrial function with age are secondary to physical inactivity. The present study investigated mitochondrial respiratory function and reactive oxygen species emission at a predefined membrane potential in young and older men subjected to 2 weeks of one-leg immobilization followed by 6 weeks of aerobic cycle training. Immobilization increased reactive oxygen species emission and decreased ATP generating respiration. Subsequent aerobic training reversed these effects. By contrast, age had no effect on the measured variables. The results of the present study support the notion that increased mitochondrial reactive oxygen species production mediates the detrimental effects seen after physical inactivity and that ageing per se does not cause mitochondrial dysfunction. Mitochondrial dysfunction, defined as increased oxidative stress and lower capacity for energy production, may be seen with ageing and may cause frailty, or it could be that it is secondary to physical inactivity.

See full abstract

Guadalupe-Grau A, Plenge U, Helbo S, Kristensen M, Andersen PR, Fago A, Belhage B, Dela F and Helge JW. Effects of an 8-weeks erythropoietin treatment on mitochondrial and whole body fat oxidation capacity during exercise in healthy males. Journal of  Sports Science. 33: 570-578, 2015.

Abstract

The present investigation was performed to elucidate if the non-erythropoietic ergogenic effect of a recombinant erythropoietin treatment results in an impact on skeletal muscle mitochondrial andwhole body fatty acid oxidation capacity during exercise, myoglobin concentration and angiogenesis. Recombinant erythropoietin was administered by subcutaneous injections (5000 IU) in six healthy male volunteers (aged 21 ± 2 years; fat mass 18.5 ± 2.3%) over 8 weeks. The participants performed two graded cycle ergometer exercise tests before and after the intervention where VO2max and maximal fat oxidation were measured. Biopsies of the vastus lateralis muscle were obtained before and after the intervention. Recombinant erythropoietin treatment increasedmitochondrial O2 flux during ADP stimulated state 3 respiration in the presence of complex I and II substrates (malate, glutamate, pyruvate, succinate) with additional electron input from β-oxidation(octanoylcarnitine) (from 60 ± 13 to 87 ± 24 pmol · s(-1) · mg(-1) P < 0.01). 

See full abstract

Hansen M, Lund MT, Gregers E, Kraunsoe R, van Hall G, Helge JW and Dela F. Adipose tissue mitochondrial respiration and lipolysis before and after a weight loss by diet and RYGB. Obesity. Accepted, 2015.

Abstract

To study adipose tissue mitochondrial respiration and lipolysis following a massiveweight loss. High resolution respirometry of adipose tissue biopsies and tracer determined whole body lipolysis. Sixteen obese patients with type 2 diabetes (T2DM) and 27 without (OB) were studied following a massive weight loss by diet and Roux-en-Y gastric bypass (RYGB).

See full abstract

Hansen M, Lund MT, Jorgensen AL, Palsoe MK, van Hall G, Helge JW and Dela F. The effects of diet- and RYGB-induced weight loss on insulin sensitivity in obese patients with and without type 2 diabetes. Acta Diabetology. Accepted, 2015.

Abstract

The impact of diet-induced weight loss and weight loss due to RYGB in patients with (T2DM, N = 16) and without (OB, N = 27) type 2 diabetes was studied. At inclusion (A), after diet-induced weight loss (B), 4 months post-surgery (C) and 18 months post-surgery (D) body composition, hepatic glucose production (HGP), insulin-mediated glucose uptake (GIR), respiratory exchange ratio, hepatic insulin sensitivity and clearance were determined. GLUT4, intramuscular triglycerides (IMTG) and glycogen content were measured in skeletal muscle.

See full abstract

Hansen M, Palsøe MK, Helge JW, Dela F. The Effect of Metformin on Glucose Homeostasis During Moderate Exercise. Diabetes Care.  38: 293-301, 2015.

Abstract

We investigated the role of metformin on glucose kinetics during moderate exercise. Before, during, and after a 45-min bout of exercise at 60% VO2max, glucose kinetics were determined by isotope tracer technique in patients with type 2 diabetes mellitus with metformin treatment (DM2+Met) or without metformin treatment (DM2) and in healthy control subjects (CON) matched for BMI and age. Glucoregulatory hormones and metabolites were measured throughout the study.

See full abstract

Herchenhan A, Bayer ML, Eliasson P, Magnusson SP and Kjaer M. Insulin-like growth factor I enhances collagen synthesis in engineereded human tendon tissue. Growth Hormone IGF Research. 25: 13-19, 2015.

Abstract

Isolated human tendon cells form 3D tendon constructs that demonstrate collagenfibrillogenesis and feature structural similarities to tendon when cultured under tensile load. The exact role of circulating growth factors for collagen formation in tendon is sparsely examined. We investigated the influence of insulin-like growth factor I (IGF-I) on tendon construct formation in 3D cell culture.Tendon constructs were grown in 0.5 or 10% FBS with or without IGF-I (250 mg/ml) supplementation. Collagen content (fluorometric), mRNA levels (PCR) and fibril diameter (transmission electron microscopy) were determined at 7, 10, 14, 21 and 28 days.

See full abstract

Hershenhan A, Uhlenbrock F, Eliasson P, Weis MA, Eyre D, Kadler KE, Magnusson SP and Kjaer M. Lysyl Oxidase activity is required for ordered collagen fibrillogenesis by tendon cells. Journal of Biological Chemistry. 290: 16440-50, 2015.

Abstract

Lysyl oxidases (LOXs) are a family of copper-dependent oxido-deaminases that can modify the side chain of lysyl residues in collagen and elastin, thereby leading to the spontaneous formation of non-reducible aldehyde-derived interpolypeptide chain cross-links. The consequences of LOX inhibition in producing lathyrism are well documented, but the consequences on collagen fibril formation are less clear. Here we used β-aminoproprionitrile (BAPN) to inhibit LOX in tendon-like constructs (prepared from human tenocytes), which are an experimental model of cell-mediatedcollagen fibril formation. The improvement in structure and strength seen with time in control constructs was absent in constructs treated with BAPN. As expected, BAPN inhibited the formation of aldimine-derived cross-links in collagen, and the constructs were mechanically weak. 

See full abstract

Hey-Mogensen M, Gram M, Jensen MB, Lund MT, Hansen CN, Scheibye-Knudsen M, Bohr VA and Dela F. A novel method for determining human ex vivo submaximal skeletal muscle mitochondrial function. Journal of Physiology. 593: 3991-4010, 2015.

Abstract

The present study utilized a novel method aiming to investigate mitochondrial function in humanskeletal muscle at submaximal levels and at a predefined membrane potential. The effect of age and training status was investigated using a cross-sectional design. Ageing was found to be related to decreased leak regardless of training status. Increased training status was associated with increased mitochondrial hydrogen peroxide emission. Despite numerous studies, there is no consensus about whether mitochondrial function is altered with increased age. The novelty of the present study is the determination of mitochondrial function at submaximal activity rates, which is more physiologically relevant than the ex vivo functionality protocols used previously. Musclebiopsies were taken from 64 old or young male subjects (aged 60-70 or 20-30 years). Aged subjects were recruited as trained or untrained. Muscle biopsies were used for the isolation of mitochondria and subsequent measurements of DNA repair, anti-oxidant capacity and mitochondrialprotein levels (complexes I-V). Mitochondrial function was determined by simultaneous measurement of oxygen consumption, membrane potential and hydrogen peroxide emission using pyruvate + malate (PM) or succinate + rotenone (SR) as substrates. 

See full abstract

Holm C, Kjaer M and Eliasson P. Achilles tendon rupture – treatment and complications: A systematic review. Scandinavian Journal of Medicine and Science in Sports. 25: e1-10, 2015.

Huang T, Larsen KT, Jepsen JR, Møller NC, Thorsen AK, Mortensen EL, Andersen LB. Effects of an obesity intervention program on cognitive function in children: A randomized controlled trial. Obesity. 23: 2101-2108, 2015.

Abstract

Adiposity may be associated with poorer cognitive function in children. The purpose of the study was to examine the effects of an obesity intervention on cognitive function in children. One hundred and fifteen children were randomly allocated to either the Day CampIntervention Arm (DCIA) or the Standard Intervention Arm (SIA). Children in the DCIA participated in a 6-week day camp intervention and a subsequent 46-week family-based intervention. The campintervention mainly consisted of physical exercise and health classes. The SIA was offered one weekly physical exercise session for 6 weeks and one educational meeting. Anthropometrics andcognitive function were measured at baseline, 6 weeks, and 52 weeks.

See full abstract

Husemoen LL, Ebstrup JF, Mortensen EL, Schwarz P, Skaaby T, Thuesen BH, Jørgensen T, Linneberg A. Serum 25-hydroxyvitamin D and self-reported mental health status in adult Danes. European Journal of Clinical Nutrition. 70(1):78-84, Accepted, 2015.

Abstract

Vitamin D receptors and vitamin D-metabolising enzymes are present in the brain and in the central nervous system at sites responsible for the regulation of emotions and behaviour. This raises the hypothesis that low vitamin D is related to poor mentalhealth. Our aim was to examine the association between serum 25-hydroxyvitamin D (25(OH)D) and the self-reported symptoms and diagnosis of depression and anxiety in the adult general population. Serum 25(OH)D was measured in three Danish population-based studies, including 5308 adults aged 18-64 years. After 5 years, 2004 participants were re-examined. Symptoms of depression and anxiety were assessed by the Symptom Check List (SCL)-90-R, andself-reported doctor-diagnosed depression and anxiety was recorded by using a questionnaire.

See full abstract

Jennum P, Ibsen R and Kjellberg J. Health, social and economic consequences of polyneuropathy: a controlled national study evaluating societal effects on patients and their partners. European Neurology. 73: 81-8, 2015.

Abstract

To estimate the direct and indirect factual costs of polyneuropathy in a national sample ofpatients and their spouses based on a national register-based cohort study with matched controls.

Using records from the Danish National Patient Registry (1997-2009) all patients with a diagnosis of polyneuropathy and their partners were identified and compared with randomly chosen controls matched for age, gender, geographic area and civil status. Direct costs included frequencies of primary and secondary sector contacts and procedures, and medication. Indirect costs included the effect on labor supply. Social-transfer payments were included to illustrate the effect on national accounts. All cost data were extracted fromnational databases.

See full abstract

Jensen RB, Juul A, Larsen T, Mortensen EL and Greisen G.  Cognitive ability in adolescents born small for gestational age: Associations with fetal growth velocity, head circumference and postnatal growth. Early Human Development. 91(12): 755-60, 2015.

Abstract

Small size at birth may be associated with impaired cognitive ability later in life. The aim of this study was to examine the effect of being born small for gestational age (SGA), with or without intrauterinegrowth restriction (IUGR) on cognitive ability in late adolescence.

A follow-up study of a former cohort included 123 participants (52 males); 47 born SGA and 76 born appropriate for gestational age (AGA). Fetal growth velocity (FGV) was determined by serial ultrasound measurements during the third trimester. A control group matched for age and birthplace was included. The original Wechsler Adult Intelligence Scale (WAIS) was administered, and verbal, performance and full-scale Intelligence Quotient (IQ) scores were calculated.

See full abstract

Jessen SB, Brazhe A, Lind BL, Mathiesen C, Thomsen K, Jensen K and Lauritzen M. GABAA Receptor-Mediated Bidirectional Control of Synaptic Activity, Intracellular Ca2+, Cerebral Blood Flow, and Oxygen Consumption in Mouse Somatosensory Cortex In Vivo. Cerebral Cortex. 25: 2594-609, 2015.

Abstract

Neural activity regulates local increases in cerebral blood flow (ΔCBF) and the cortical metabolic rate ofoxygen (ΔCMRO2) that constitutes the basis of BOLD functional neuroimaging signals. Glutamate signaling plays a key role in brain vascular and metabolic control; however, the modulatory effect of GABA is incompletely understood. Here we performed in vivo studies in mice to investigate how THIP (which tonically activates extrasynaptic GABAARs) and Zolpidem (a positive allosteric modulator of synaptic GABAARs) impact stimulation-induced ΔCBF, ΔCMRO2, local field potentials (LFPs), and fluorescent cytosolic Ca(2+) transients in neurons and astrocytes. Low concentrations of THIP increased ΔCBF and ΔCMRO2 at low stimulation frequencies. These responses were coupled to increased synaptic activity as indicated by LFP responses, and to Ca(2+) activities in neurons and astrocytes. 

See full abstract

Jessen SB, Mathiesen C, Lind BL and Lauritzen M. Interneuron Deficit Associates Attenuated Network Synchronization to Mismatch of Energy Supply and Demand in Aging Mouse Brains. Cerebral Cortex. 29: pii: bhv261. [Epub ahead of print], 2015.

Abstract

Higher cognitive functions depend critically on synchronized network activity in the gamma range (30-100 Hz), which results from activity of fast-spiking parvalbumin-positive (PV) interneurons. Here, we examined synaptic activity in the gamma band in relation to PV interneuron activity, stimulation-induced calcium activity in neurons and astrocytes, and cerebral blood flow and oxygen responses in the somatosensory cortex of young adult and old adult mice in vivo using electrical whisker pad stimulation. Gamma activity was reduced in old adult mice, and associated with reduced calcium activity of PV interneurons, whereas the overall responses of neurons and astrocytes were unchanged. Hemodynamic responses were highly correlated to the power of synaptic activity in both young adult and old adult mice, but the hemodynamic response amplitude attained was lower in old adult mice.

See full abstract

Karlsen A, Couppé C, Andersen JL, Mikkelsen UR, Nielsen RH, Magnusson P, Kjaer M and Mackey AL. Matters of fiber size and myonuclear domain; does size matter more than age? Muscle Nerve. Accepted, 2015.

Abstract

The relationship between fiber size and myonuclear content is poorly understood.

Biopsy cross-sections from young and old trained and untrained healthy individuals were analyzed for fiber area and myonuclei, and 2 fiber-size-dependent cluster analyses were performed.

See full abstract

Kesmodel US, Kjaersgaard MIS, Denny CH, Bertrand J, Skogerbø Å, Eriksen HF, Bay B, Underbjerg M and Mortensen EL. The association of pre-pregnancy alcohol drinking with child neuropsychological functioning. BJOG. 122: 1728-1738, 2015.

Abstract

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

See full abstract

Kjaer M, Jørgensen NR, Heinemeier K and Magnusson SP. Exercise and regulation of bone and collagen tissue biology. Progress in Molecular Biolology and Translational Science. 135: 259-291, 2015.

Abstract

The musculoskeletal system and its connective tissue include the intramuscular connective tissue, the myotendinous junction, the tendon, the joints with their cartilage and ligaments, and the bone; they all together play a crucial role in maintaining the architecture of the skeletal muscle, ensuring force transmission, storing energy, protecting joint surface and stability, and ensuring the transfer of muscular forces into resulting limb movement. The musculoskeletal connective tissue structure is relatively stable, but mechanical loading and subsequent mechanotransduction and molecular anabolic signaling can result in some adaptation of the connective tissue, its size, its strength, and its mechanical properties, whereby it can improve its capacity by 5-20% with regular physical activity. For several of the mechanically loaded connective tissues, only limited information regarding molecular and cellular signaling pathways and their adaptation to exercise is available. 

See full abstract

Knudsen GM, Jensen PS, Erritzoe D, Baaré WF, Ettrup A, Fisher PM, Gillings N, Hansen HD, Hansen LK, Hasselbalch SG, Henningsson S, Herth MM, Holst KK, Iversen P, Kessing LV, Macoveanu J, Madsen KS, Mortensen EL, Nielsen FÅ, Paulson OB, Siebner HR, Stenbæk DS, Svarer C, Jernigan TL, Strother SC and Frokjaer VG.  The Center for Integrated Molecular Brain Imaging (Cimbi) database. Neuroimage.  Epub: April 17, 2015.

Abstract

We here describe a multimodality neuroimaging containing data from healthy volunteers and patients, acquired within the Lundbeck Foundation Center for Integrated Molecular Brain Imaging (Cimbi) in Copenhagen, Denmark. The data is of particular relevance for neurobiological research questions related to the serotonergic transmitter system with its normative data on the serotonergic subtype receptors 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4 and the 5-HT transporter (5-HTT), but can easily serve other purposes. The Cimbi database andCimbi biobank were formally established in 2008 with the purpose to store the wealth of Cimbi-acquired data in a highly structured and standardized manner in accordance with the regulations issued by the Danish Data Protection Agency as well as to provide a quality-controlled resource for future hypothesis-generating and hypothesis-driven studies.

See full abstract

Kilburn TR, Eriksen HF, Underbjerg M, Thorsen P, Mortensen EL, Landrø NI, Bakketeig LS, Grove J, Sværke C and Kesmodel US. Low to Moderate Average Alcohol Consumption and Binge Drinking in Early Pregnancy: Effects on Choice Reaction Time and Information Processing Time in Five-Year-Old Children. PLoS One. 10(9): e0138611, 2015.

Abstract

Deficits in information processing may be a core deficit after fetal alcohol exposure. This study was designed to investigate the possible effects of weekly low to moderate maternal alcoholconsumption and binge drinking episodes in early pregnancy on choice reaction time (CRT) and informationprocessing time (IPT) in young children. Participants were sampled based on maternal alcohol consumption during pregnancy. At the age of 60-64 months, 1,333 children were administered a modified version of the Sternberg paradigm to assess CRT and IPT. In addition, a test of general intelligence (WPPSI-R) was administered.

See full abstract

Knudsen AB, Larsen M, Mackey AL, Hjort M, Hansen KK, Qvortrup K, Kjaer M and Krogsgaard MR. The human myotendinous junction: An ultrastructural and a 3D analysis study. Scandinavian Journal of Medicine and Science in Sports. 25: 116-23, 2015.

Abstract

The myotendinous junction (MTJ) is a specialized structure in the musculotendinous system, where force is transmitted from muscle to tendon. Animal models have shown that the MTJ takes form of tendon finger-like processes merging with muscle tissue. The human MTJ is largely unknown and has never been described in three dimensions (3D). The aim of this study was to describe the ultrastructure of the human MTJ and render3D reconstructions. Fourteen subjects (age 25 ± 3 years) with isolated injury of the anterior cruciate ligament (ACL), scheduled for reconstruction with a semitendinosus/gracilis graft were included. Semitendinosus and gracilis tendons were stripped as grafts for the ACL reconstruction. The MTJ was isolated from the grafts and prepared for transmission electron microscopy (TEM) and focused ion beam/scanning electron microscopy. It was possible to isolate recognizable MTJ tissue from all 14 patients.

See full abstract

Kosters A, Potzelsberger B, Dela F, Dorn U, Hofstaedter T, Fink C and Muller E. Alpine Skiing With total knee ArthroPlasty (ASWAP): study design and intervention. Scandinavian Journal of Medicine & Science in Sports. 25(2): 3-9, 2015.

Abstract

The aim of this study was to monitor the long-term effects of skiing on health-related parameters and implant related factors like loosening and wear in patients with total knee arthroplasty. This paper describes the overall study design, general demographics, and physiological demand of the intervention phase. A control group design consisting of an intervention group (n = 14; age: 70.4 ± 4.5 years) and a control group (n = 17; age: 71.5 ± 5.1 years) was utilized in this study. Parameters of interest were measured during pre-, post-, and retention test sessions. During the 12 weeks of intervention, an average of 25.5 days of guided skiing was conducted by each patient. Daily heart rate (HR) profiles and global positioning system data throughout the ski day were recorded. 

See full abstract

Kriegbaum M, Hendriksen C, Vass M, Mortensen EL and Osler, M. Hypnotics and mortality – confounding by disease and socioeconomic position? Pharmacoepidemiology and Drug Safety. 24:  779-783, 2015. 

Abstract

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

See full abstract

Kristensen DE, Albers PH, Prats C, Baba O, Birk JB and Wojtaszewski JF. J Human muscle fibre type-specific regulation of AMPK and downstream targets by exercise. Physiology. 593: 2053-69, 2015. 

Abstract

AMP-activated protein kinase (AMPK) is a regulator of energy homeostasis during exercise. Studies suggestmuscle fibre type-specific AMPK expression. However, fibre type-specific regulation of AMPK anddownstream targets during exercise has not been demonstrated. We hypothesized that AMPK subunits are expressed in a fibre type-dependent manner and that fibre type-specific activation of AMPK and downstreamtargets is dependent on exercise intensity. Pools of type I and II fibres were prepared from biopsies of vastus lateralis muscle from healthy men before and after two exercise trials: (1) continuous cycling (CON) for 30 min at 69 ± 1% peak rate of O2 consumption (V̇O2 peak ) or (2) interval cycling (INT) for 30 min with 6 × 1.5 min high-intensity bouts peaking at 95 ± 2% V̇O2 peak . In type I vs. II fibres a higher β1 AMPK (+215%) and lower γ3 AMPK expression (-71%) was found. α1 , α2 , β2 and γ1 AMPK expression was similar betweenfibre types.

See full abstract

Kristensen MM, Helge JW and Dela F. Comment on Rezen et al. Expression changes in human skeletal muscle miRNAs following 10 days of bed rest in young healthy males. Acta Physiology. 214: 157, 2015.

Kristensen M, Potzelsberger B, Scheiber P, Bergdahl A, Hansen CN, Andersen JL, Narici M, Salvioli S, Conte M, Muller E and Dela F. Alpine Skiing With total knee ArthroPlasty (ASWAP): metabolism, inflammation, and skeletal muscle fiber characteristics. Scandinavian Journal of Medicine & Science in Sports. 25 (2): 40-48, 2015.

Abstract

We investigated the effect of alpine skiing for 12 weeks on skeletal muscle characteristics and biomarkers of glucose homeostasis and cardiovascular risk factors. Twenty-three patients with a total knee arthroplasty(TKA) were studied 2.9 ± 0.9 years (mean ± SD) after the operation. Fourteen patients participated in the intervention group (IG) and nine in the control group (CG). Blood samples and muscle biopsies were obtained before (PRE) and 7.3 ± 0.8 days after (POST) the intervention, and blood samples again after a retention (RET) phase of 8 weeks. With skiing, glucose homeostasis improved in IG (decrease in fasting insulin, increase in muscle glycogen) but not in CG.

See full abstract

Larsen S, Danielsen JH, Sondergard SD, Sogaard D, Vigelsoe A, Dybboe R, Skaaby S, Dela F and Helge JW. The effect of high-intensity training on mitochondrial fat oxidation in skeletal muscle and subcutaneous adipose tissue. Scandinavian Journal of Medicine & Science in Sports. 25: 59-69, 2015.

Abstract

High-intensity interval training (HIT) is known to increase mitochondrial content in a similar way as endurancetraining [60-90% of maximal oxygen uptake (VO2peak)]. Whether HIT increases the mitochondria's ability to oxidize lipids is currently debated. We investigated the effect of HIT on mitochondrial fat oxidation in skeletalmuscle and adipose tissue. Mitochondrial oxidative phosphorylation (OXPHOS) capacity, mitochondrialsubstrate sensitivity (K(m)(app)), and mitochondrial content were measured in skeletal muscle and adiposetissue in healthy overweight subjects before and after 6 weeks of HIT (three times per week at 298 ± 21 W). HIT significantly increased VO2peak from 2.9 ± 0.2 to 3.1 ± 0.2 L/min. No differences were seen in maximalfat oxidation in either skeletal muscle or adipose tissue. 

See full abstract

Larsen S, Scheede-Bergdahl C, Whitesell T, Boushel R and Bergdahl A. Increased intrinsic mitochondrial respiratory capacity in skeletal muscle from rats with streptozotocin-induced hyperglycemia. Physiological Reports. Accepted, 2015.

Abstract

Type I diabetes mellitus (T1DM) is a chronic disorder, characterized by an almost or complete insulin deficiency. Widespread tissue dysfunction and deleterious diabetes-complications are associated with long-term elevations of blood glucose. The aim of this study was to investigate the effects of type I diabetes, as induced by streptozotocin, on the mitochondria in skeletal muscles that predominantly consist of either slow or fast twitch fibers. Soleus (primarily slow twitch fiber type) and the plantaris muscle (mainly fast twitch fiber type) were removed in order to measure mitochondrial protein expression and integrated mitochondrialrespiratory function. Mitochondrial capacity for oxidative phosphorylation (OXPHOS) was found to be higher in the slow (more oxidative) soleus muscle from STZ rats when evaluating lipid and complex I linked OXPHOScapacity, whereas no difference was detected between the groups when evaluating the more physiological complex I and II linked OXPHOS capacity.

See full abstract

Lenskjold A, Kongsgaard M, Larsen JO, Nielsen RH, Kovanen V, Aagaard P, Kjaer M, Magnusson SP. The influence of physical activity during youth on structural and functional properties of the Achilles tendon. Scandinavian  Journal of Medicine and Science in Sports. 25: 25-31, 2015.

Abstract

Achilles tendinopathy is a highly prevalent sports injury. Animal studies show a growth response in tendons in response to loading in the immature phase but not after puberty maturation. The aim of this investigation was to examine the structural and material properties in long distance runners who were either physically active (HAY) or inactive (LAY) in young age. Twelve men in HAY group and eight men in LAY group participated.Structural, functional, and biochemical properties of Achilles tendon were estimated from magnetic resonance imaging, ultrasound video recordings, mechanical tests, and tendon biopsies, respectively. There was no difference between the groups with respect to tendon cross-sectional area or tendon free length. There was no difference between the groups with respect to maximal force or mechanical properties. 

See full abstract

Lund MT, Hansen M, Skaaby S, Dalby S, Stockel M, Floyd AK, Bech K, Helge JW, Holst JJ and Dela F. Preoperative beta-cell function in patients with type 2 diabetes is important for the outcome of Roux-en-Y gastric bypass surgery. Journal of Physiology. 593: 3123-3133, 2015.

Abstract

The majority of the patients with type 2 diabetes (T2DM) show remission after Roux-en-Y gastric bypass(RYGB). This is the result of increased postoperative insulin sensitivity and β-cell secretion. The aim of the present study was to elucidate the importance of the preoperative β-cell function in T2DM for the chance of remission after RYGB. Fifteen patients with and 18 without T2DM had 25 g oral (OGTT) and intravenous (IVGTT) glucose tolerance tests performed at inclusion, after a diet-induced weight loss, and 4 and 18 months after RYGB. Postoperative first phase insulin secretion rate (ISR) during the IVGTT and β-cell glucose sensitivity during the OGTT increased in T2DM. Postoperative insulin sensitivity and the disposition index (DI) markedly increased in both groups. By stratifying the T2DM into two groups according to highest (T2DMhigh ) and lowest (T2DMlow ) baseline DI, a restoration of first phase ISR and β-cell glucose sensitivity were seen only in T2DMhigh.

See full abstract

Lund MT, Hansen M, Wimmelmann CL, Taudorf LR, Helge JW, Mortensen EL and Dela F. Increased post-operative cardiopulmonary fitness in gastric bypass patients is explained by weight loss. Scandinavian Journal of Medicine & Science in Sports. Accepted, 2015.

Abstract

Roux-en-Y gastric bypass (RYGB) leads to a major weight loss in obese patients. However, given that mostpatients remain obese after the weight loss, regular exercise should be part of a healthier lifestyle. The primary aim of this study was to investigate the cardiopulmonary fitness in obese patients before and after RYGB. Thirty-four patients had body composition and cardiopulmonary fitness (VO2max ) assessed and completed questionnaires regarding physical activity and function twice before RYGB (time points A and B) and 4 and 18 months after surgery (time points C and D). Weight loss was 37 ± 2 kg during the study period. VO2max increased (A: 21 ± 1 vs D: 29 mL/min/kg, P < 0.001), but absolute VO2max decreased (A: 2713 ± 126 vs 2609 ± 187 mL/min, P = 0.02) and VO2max per kilogram fat free mass did not change. 

See full abstract

Lund R, Mortensen EL, Christensen U, Bruunsgaard H, Holm-Pedersen P, Fiehn NE, Molbo D, Jepsen E, Hansen ÅM and Osler M. Cohort Profile: The Copenhagen Aging and Midlife Biobank (CAMB). International Journal of Epidemiology. 25. pii: dyv149, 2015.

Masters Pedersen J, Budtz Jorgensen E, Mortensen EL, Bruunsgaard H, Osler M, Sørensen TIA, Rod NH and Lund R.  Late midlife C-reactive protein and interleukin-6 in relation to body weight history within and across generations.  Obesity. Accepted, 2015.

Abstract

The aim was to estimate the effects of ponderal index at birth and body mass index (BMI) in early adulthood on C-reactive protein (CRP) and interleukin-6 (IL-6) and to quantify the effects through subsequent measures of body size. In a sub analysis, the contributions of maternal BMI to the inflammatory status of offspring were investigated. The study was based on 2,986 Danish males from the Copenhagen Aging and Midlife Biobank. Path analysis was employed to estimate direct and indirect effects.

See full abstract

Masters Pedersen J, Rod NH, Lange T, Poulsen G, Prescott E, Andersen I, Lund R. Accumulation of major life events in childhood and adult life and risk of type 2 diabetes mellitus. Plos One. 22;10(9):e0138654, 2015.

Abstract

The aim of the study was to estimate the effect of the accumulation of major life events(MLE) in childhood and adulthood, in both the private and working domains, on risk of type 2 diabetes mellitus(T2DM). Furthermore, we aimed to test the possible interaction between childhood and adult MLE and to investigate modification of these associations by educational attainment.

The study was based on 4,761 participants from the Copenhagen City Heart Study free of diabetes at baseline and followed for 10 years. MLE were categorized as 0, 1, 2, 3 or more events. Multivariate logistic regression models adjusted for age, sex, education and family history of diabetes were used to estimate the association between MLE and T2DM.

See full abstract

Meincke RH, Osler M, Mortensen EL and Hansen ÅM. Is Intelligence in Early Adulthood Associated With Midlife Physical Performance Among Danish Males? Journal of Aging and Health. 28(3): 530-45, 2015.

Abstract

Insights into the causes of variances in physical performance are important to prevent mobility limitations in old age. We examined associations between intelligence in early adulthood and midlife physicalperformance. Data from the Copenhagen Aging and Midlife Biobank were analyzed using linear regression. In total, 2,848 male cohort members had intelligence scores from conscription and physical performancemeasures from midlife.

See full abstract

Mikkelsen SS, Tolstrup JS, Becker U, Mortensen EL and Flensborg-Madsen T. Social network as predictor for onset of alcohol use disorder: A prospective cohort study. Comprehensive  Psychiatry. 61: 57-63, 2015. 

Abstract

Social network has been linked to alcohol use disorder in several studies. However, since the majority of such findings are cross-sectional, causal interpretation is difficult. The aim of the present studywas to test if social network characteristics predict alcohol use disorder in a prospective design. Information on social network and covariates was obtained from 9589 men and women aged 21-99 years in the Copenhagen City Heart Study, followed for registration of alcohol use disorder in the Danish National Patient Registry and the WINALCO database.

See full abstract

Mikkelsen UR, Dideriksen K, Andersen MB, Boesen A, Malmgaard-Clausen NM, Sørensen IJ, Schjerling P, Kjaer M and Holm L. Preserved skeletal muscle protein anabolic response to acute exercise and protein intake in well-treated rheumatoid arthritis patients. Arthritis Research & Therapy. 17: 271-281, 2015.

Abstract

Rheumatoid arthritis (RA) is often associated with diminished muscle mass, reflecting an imbalance between protein synthesis and protein breakdown. To investigate the anabolic potential of bothexercise and nutritional protein intake we investigated the muscle protein synthesis rate and anabolicsignaling response in patients with RA compared to healthy controls. Thirteen RA patients (age range 34-84 years; diagnosed for 1-32 years, median 8 years) were individually matched with 13 healthy controls for gender, age, BMI and activity level (CON). Plasma levels of C-reactive protein (CRP), interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured using enzyme-linked immunosorbent assay (ELISA) in resting blood samples obtained on two separate days. Skeletalmuscle myofibrillar and connective tissue protein fractional synthesis rate (FSR) was measured by incorporation of the amino acid (13)C6-phenylalanine tracer in the overnight fasted state for 3 hours (BASAL) and 3 hours after intake of whey protein (0.5 g/kg lean body mass) alone (PROT, 3 hrs) and in combination with knee-extensor exercise (EX) with one leg (8 × 10 reps at 70 % of 1RM; PROT + EX, 3 hrs). Expression of genes related to inflammatory signaling, myogenesis and muscle growth/atrophy were analyzed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR).

See full abstract

Moeller SB, Bech P, Kessing L, Mortensen EL, Stephen F and Bukh, JOD. A Psychometric  Validation Analysis of Eysenck’s Neuroticism and Extraversion Scales in a Sample of First Time Depressed Patients. Journal of Depression and Anxiety. 4: 202, 2015.

Mortensen EL. Life course consequences of breastfeeding (invited comment). Lancet Global Health. 3: 179-180, 2015.

Narici M, Conte M, Salvioli S, Franceschi C, Selby A, Dela F, Rieder F, Kosters A and Muller E. Alpine Skiing With total knee ArthroPlasty (ASWAP): impact on molecular and architectural features of musculo-skeletal ageing. Scandinavian Journal of Medicine & Science in Sports. 25(2):  33-39, 2015.

Abstract

This study investigated features of skeletal muscle ageing in elderly individuals having previously undergone unilateral total knee arthroplasty (TKA) and whether markers of sarcopenia could be mitigated by a 12-weekalpine skiing intervention. Novel biomarkers agrin, indicative of neuromuscular junction (NMJ) degeneration, tumor suppressor protein p53, associated with muscle atrophy, and a new ultrasound-based muscle architecture biomarker were used to characterize sarcopenia. Participant details and study design are presented by Kösters et al. (2015). The results of this study show that NMJ degeneration is widespread among active septuagenarians previously subjected to TKA: all participants showed elevated agrin levels upon recruitment.

See full abstract

Nordbrandt MS, Carlsson J, Lindberg LG, Sandahl H, Mortensen EL. Treatment of traumatised refugees with basic body awareness therapy versus mixed physical activity as add-on treatment: Study protocol of a randomised controlled trial. Trials. 16(1): 477, 2015.

Treatment of traumatised refugees is one of the fields within psychiatry, which has received little scientific attention. Evidence based treatment and knowledge on the efficiency of the treatment for this complex patient group is therefore scarce. This leads to uncertainty as to which treatment should be offered and potentially lowers the quality of life for the patients. Chronic pain is very common among traumatisedrefugees and it is believed to maintain the mental symptoms of trauma. Hence, treating chronic pain is believed to be of high clinical value for this patient group. In clinical studies, physical activity has shown a positive effect on psychiatric illnesses such as depression and anxiety and for patients with chronic pain. However, scientific knowledge about physical activity as part of the treatment for traumatised refugees is very limited and no guidelines exist on this topic.

See full abstract

Nordby P, Rosenkilde M, Ploug T, Helge JW, Westh K, Feigh M and Stallknecht B. Independent effects of endurance training and weight loss on peak fat oxidation in moderately overweight men: a randomized controlled trial. Journal of Applied Physiology.118: 803-810, 2015.

Abstract

Endurance training increases peak fat oxidation (PFO) during exercise, but whether this is independent of changes in body weight is not known. The aim of the present study was to investigate the effects ofendurance training with or without weight loss or a diet-induced weight loss on PFO and on key skeletal muscle mitochondrial proteins involved in fat oxidation. Sixty moderately overweight, sedentary but otherwise healthy men were randomized to 12 wk of training (T), diet (D), training and increased caloric intake (T-iD), or continuous sedentary control (C). Isoenergetic deficits corresponding to 600 kcal/day were comprised ofendurance exercise for T and caloric restriction for D. T-iD completed similar training but was not in 600 kcal deficit because of dietary replacement. PFO and the exercise intensity at which this occurred (FatMax) were measured by a submaximal exercise test and calculated by polynomial regression. 

See full abstract

Norup A, Kristensen KS, Poulsen I, Mortensen EL. Evaluating clinically significant changes in health-related quality of life: A sample of relatives of patients with severe traumatic brain injury. Neuropsychological Rehabilitation. 24:1-20, 2015.

Abstract

The objective of the study was to investigate change and predictors of change in health-related quality of life(HRQoL) in relatives of patients with severe traumatic brain injury (TBI) during rehabilitation, and to analyse associations between changes in HRQoL and symptoms of anxiety and depression. The Vitality (VT), Mental Health (MH), Social Function (SF) and the Role Emotional (RE) scales from the Short Form 36, and the anxiety and depression scales from the Symptom Checklist-90 - Revised were used. Of the 62 relatives, 24.6% experienced a reliable improvement on the VT scale, 53.2% on the MH scale, 27.4% on the SF scale and 16.1% on the RE scale. 

See full abstract

Norup A and Mortensen EL. Prevalence and Predictors of Personality Change after Severe Brain Injury. Archives Physical Medicine and Rehabilitation. 96: 56-62, 2015.

Abstract

To investigate the prevalence of personality change after severe brain injury; to identifypredictors of personality change; and to investigate whether personality change is associated with distress in family members.

See full abstract

Norup A, Petersen J, Siert L and Mortensen EL. Relatives of Patients with Severe Brain Injury: Growth Curve Analysis of Anxiety and Depression the First Year after Injury. Brain Injury. 29: 822-829, 2015.

Abstract

To investigate trajectories and predictors of trajectories of anxiety and depression inrelatives of patients with a severe brain injury during the first year after injury. A prospective longitudinal study with four repeated measurements. Ninety relatives of patients with severe brain injury. The relatives were assessed on the anxiety and depression scales from the Symptom Checklist-90-Revised and latent variable growth curve models were used to model the trajectories. The effects of patient's age, patient's Glasgow Coma Score, level of function and consciousness, gender and relationship of the relatives were modelled.

See full abstract

Norregaard J, Gram M, Vigelsoe A, Wiuff C, Kuhlman AB, Helge JW and Dela F. The Effect of Reduced Physical Activity and Retraining on Blood Lipids and Body Composition in Young and Older Adult Men. Journal of Aging and Physical Activity. 23: 489-495, 2015.

Abstract

We studied the effect of physical inactivity and subsequent retraining on cardiovascular risk factors in 17young (Y; 23.4 ± 0.5 years) and 15 older adult (O; 68.1 ± 1.1 years) men who underwent 14 days of one leg immobilization followed by six weeks of training. Body weight remained unchanged. Daily physical activitydecreased by 31 ± 9% (Y) and 37 ± 9% (O) (p < .001). Maximal oxygen uptake decreased with inactivity (Y) and always increased with training. Visceral fat mass decreased (p < .05) with training. Concentrations oflipids in blood were always highest in the older adults. 

See full abstract

Odlaug BL, Lust K, Wimmelmann CL, Chamberlain SR, Mortensen EL, Derbyshire K, Christenson G and Grant JE.  Prevalence and correlates of being overweight or obese in college. Psychiatry Research. 27: 58-64, 2015.

Osler M, Rostrup E, Nordentoft M, Mortensen EL, Bruunsgaard H and Fagerlund B. Influence of early life characteristics on psychiatric admissions and impact of psychiatric disease on inflammatory biomarkers and survival: a Danish cohort study. World Psychiatry. 14: 364-5, 2015.

Ponce-González JG, Ara I, Larsen S, Guerra B, Calbet JAL, and Helge JW. Biogenesis regulating proteins in human skeletal muscle and obesity. Effect of regional muscle location but not adiposity on mitochondrial biogenesis regulating proteins. European Journal of Applied Physiology. Accepted, 2015.

Ponsaing LB, Iversen HK, Jennum P. Sleep apnea diagnosis varies with the hypopnea criteria applied. Sleep and Breathing. Epub ahead of print: June 13, 2015.

Abstract

We aimed to evaluate the three hypopnea criteria, A and B from 2007 and the revised from 2012, proposed by the American Academy of Sleep Medicine (AASM) for scoring sleep-related breathing disorders (SRBDs) in patients with acute stroke or transient ischemic attack (TIA). Polysomnographies (PSGs) in patients with TIA or stroke were scored according to the A-, B-,and 2012-hypopnea criteria.

See full abstract

Rasmussen MU, Rydahl-Hansen S, Amris K, Samsoe BD and Mortensen EL. The adaptation of a Danish version of the Pain Self-Efficacy Questionnaire: Reliability and construct validity and in a population of patients with fibromyalgia in Denmark. Scandinavian Journal of Caring Sciences. Epub ahead of print: Apr 29, 2015.

Abstract

The aim of this study was to translate, culturally adapt and evaluate the psychometric properties of the PainSelf-Efficacy Questionnaire (PSEQ) in a population of patients with fibromyalgia in Denmark. The study sample included 102 patients diagnosed with fibromyalgia referred to a specialist clinic. The PSEQ was translated and adapted to a Danish setting using a standard stepw-ise forward-backward translation procedure, followed by initial testing and focus group interview. Reliability was examined by analysing internal consistency and test-retest agreement. Construct validity was exami-ned by investigating dimensionality, targeting, local independence, category functioning and differential item functioning (DIF). 

See full abstract

Reihmane D, Gram M, Vigelsø A, Helge JW and Dela F. Exercise promotes IL-6 release from legs in older men with minor response to unilateral immobilization European Journal of Sport Science. Accepted, 2015.

Revsbech R, Mortensen EL, Owen G, Nordgaard J, Jansson L, Sæbye D, Flensborg-Madsen T and Parnas J. Exploring rationality in schizophrenia. British Journal of Psychiatry Open. 1: 98-103, 2015. 

Abstract

Although the very idea that the generative disorder in schizophrenia is a disturbance of the self is as old as the schizophrenia concept itself, empirical studies have only recently emerged, documenting that anomalous self-experiences (i.e. self-disorders, SDs) aggregate in schizophrenia spectrum disorders but not in other mental disorders. The aim of this study is to explore potential associations between SDs, neurocognitive performance, rationality and IQ in patients with schizophrenia.

The sample comprises 31 patients diagnosed with schizophrenia (DSM-IV). All patients underwent comprehensive evaluation. SDs were assessed with the Examination of Anomalous Self-Experience scale. Neurocognitive performance was measured with 4 PC-implemented subtests from the Cambridge Neuropsychological Test Automated Battery. Rationality was measured using syllogism tests. The IQ was indexed by a summary score of 4 IST-2000-R computerized subtests.

See full abstract

Rosenkilde M, Morville T, Riis AP, Kjaer K, Rasmusen H, Holst JJ, Dela F, Westerterp K, Sjodin A and Helge JW. Inability to match energy intake with energy expenditure at sustained near-maximal rates of energy expenditure in older men during a 14-d cycling expedition. American Journal of Clinical Nutrition.102: 1398-1405, 2015.

Abstract

The upper rates of energy expenditure (EE) and the corresponding regulation of energy intake(EI), as described in younger trained subjects, are not well elucidated in older subjects. The aim was to investigate EE in older men during prolonged cycling and determine whether it is sufficiently matched by EI to maintain energy balance. In addition, we investigated appetite ratings and concentrations of appetite-regulating hormones. Six men (mean ± SE age: 61 ± 3 y) completed 2706 km of cycling, from Copenhagen to Nordkapp, in 14 d. EE was measured by using doubly labeled water, and food and drink intake was recorded by the accompanying scientific staff. Energy balance was calculated as the discrepancy between EI and EE and from changes in body energy stores as derived from deuterium dilution. Fasting hormones were measured before and after cycling, and appetite ratings were recorded twice daily.

See full abstract

Sander M, Oxlund B, Jespersen A, Krasnik A, Mortensen EL, Westendorp R and Rasmussen LJ. The Challenges of Human Population Aging.  Age and Aging. 44: 185-187, 2015.

Abstract

The 20th century saw an unprecedented increase in average human lifespan as well as a rapid decline inhuman fertility in many countries of the world. The accompanying worldwide change in demographics of human populations is linked to unanticipated and unprecedented economic, cultural, medical, social, public health and public policy challenges, whose full implications on a societal level are only just beginning to be fully appreciated. Some of these implications are discussed in this commentary, an outcome of Cultures of Health and Ageing, a conference co-sponsored by the University of Copenhagen (UCPH) and the Center for Healthy Ageing at UCPH, which took place on 20-21 June 2014 in Copenhagen, Denmark. Questions discussed here include the following: what is driving age-structural change in human populations? how can we create 'age-friendly' societies and promote 'ageing-in-community'? what tools will effectively promote social engagement and prevent social detachment among older individuals? is there a risk that further extension of human lifespan would be a greater burden to the individual and to society than is warranted by the potential benefit of longer life?

See full abstract

Schiffman J, Kline E, Jameson ND, Sorensen HJ, Dodge S, Tsuji T, Mortensen EL and Mednick SA. Premorbid multivariate prediction of adult psychosis-spectrum disorder: A high-risk prospective investigation. Schizophrenia Research. 168: 74-78, 2015. 

Abstract

Premorbid prediction of psychosis-spectrum disorders has implications for both understanding etiology and clinical identification. The current study used a longitudinal high-risk for psychosis design that included children of parents with schizophrenia as well as two groups of controls (children whose parents had no mental illness, and children with at least one parent with a non-psychotic psychiatric diagnosis). Premorbidneurological factors and an indication of social function, as measured when participants were 10-13years of age, were combined to predict psychosis-spectrum disorders in adulthood. Through a combination of childhood predictors, the model correctly classified 82% (27 of 33) of the participants who eventually developed a psychosis-spectrum outcome in adulthood. With replication, multivariate premorbid prediction, including genetic risk, social, and neurological variables, could potentially be a useful complementary approach to identifying individuals at risk for developing psychosis-spectrum disorders.

See full abstract

Schiffman J, Mittal V, Kline E, Michelsen N, Ekstrøm M, Mortensen EL, Mednick S and Sørensen HJ. Childhood dyspraxia predicts adult-onset schizophrenia spectrum disorder. Development and Psychopathology. Accepted, 2015.

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

See full abstract

Søndergård S, Dela F, Helge JW and Larsen S. Actovegin, a non-prohibited drug increases oxidative capacity in human skeletal muscle. European Journal of Sport Science. Accepted, 2015.

Abstract

Actovegin, a deproteinized haemodialysate of calf blood, is suggested to have ergogenic properties, but this potential effect has never been investigated in human skeletal muscle. To investigate this purported ergogenic effect, we measured the mitochondrial respiratory capacity in permeabilized human skeletal muscle fibres acutely exposed to Actovegin in a low and in a high dose. We found that Actovegin, in the presence of complex I-linked substrates increased the oxidative phosphorylation (OXPHOS) capacity significantly in a concentration-dependent manner (19 ± 3, 31 ± 4 and 45 ± 4 pmol/mg/s). Maximal OXPHOS capacity with complex I and II-linked substrate was increased when the fibres were exposed to the high dose of Actovegin(62 ± 6 and 77 ± 6 pmol/mg/s) (p < .05). 

See full abstract

Sørensen L, Igel C, Liv Hansen N, Osler M, Lauritzen M, Rostrup E and Nielsen M. Alzheimer's Disease Neuroimaging Initiative and the Australian Imaging Biomarkers and Lifestyle Flagship Study of Ageing. Early detection of Alzheimer's disease using MRI hippocampal texture. Human Brain Mapping. Epub ahead of print: Dec 21, 2015.

Uth J, Hornstrup T, Christensen JF, Christensen KB, Jørgensen NR, Helge JW, Brasso K, Andersen LL, Rørth M, Midtgaard J and Krustrup P. Football training in men with prostate cancer undergoing androgen deprivation therapy: activity profile and short-term skeletal and postural balance adaptations.  European Journal of Applied Physiology. Accepted, 2015.

Abstract

To investigate the activity profile of football training and its short-term effects on bone mass, bone turnover markers (BTMs) and postural balance in men with prostate cancer (PCa) undergoing androgendeprivation therapy (ADT). This was a randomised 12-week study in which men with PCa undergoing ADT were assigned to a football intervention group [FTG, n = 29, 67 ± 7 (±SD) years] training 2‒3 times per week for 45‒60 min or to a control group (n = 28, 66 ± 5 years). The activity profile was measured using a 5-Hz GPS. The outcomes were total body and leg bone mineral content (BMC) and density, BTMs and postural balance.

See full abstract

Vigelso A, Dybboe R, Hansen CN, Dela F, Helge JW and Guadalupe GA. GAPDH and beta-actin protein decreases with aging, making Stain-Free technology a superior loading control in Western blotting of human skeletal muscle. Journal of Applied Physiology. 118: 386-394, 2015.

Abstract

Reference proteins (RP) or the total protein (TP) loaded is used to correct for uneven loading and/or transfer inWestern blotting. However, the signal sensitivity and the influence of physiological conditions may question the normalization methods. Therefore, three widely used reference proteins [β-actin, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and α-tubulin], as well as TP loaded measured by Stain-Free technology(SF) as normalization tool were tested. This was done using skeletal muscle samples from men subjected to physiological conditions often investigated in applied physiology where the intervention has been suggested to impede normalization (ageing, muscle atrophy, and different muscle fiber type composition). The linearity of signal and the methodological variation coefficient was obtained. Furthermore, the inter- and intraindividual variation in signals obtained from SF and RP was measured in relation to ageing, muscle atrophy, and different muscle fiber type composition, respectively.

See full abstract

Vigelso A, Gram M, Wiuff C, Andersen JL, Helge JW and Dela F. Six weeks' aerobic retraining after two weeks' immobilization restores leg lean mass and aerobic capacity but does not fully rehabilitate leg strength in young and older men. Journal of Rehabilitation Medicine. 47: 552-560, 2015.

Abstract

To determine the effect of aerobic retraining as rehabilitation after short-term leg immobilizationon leg strength, leg work capacity, leg lean mass, leg muscle fibre type composition and leg capillary supply, in young and older men.Subjects and design: Seventeen young (23 ± 1 years) and 15 older (68 ± 1 [standard error of the mean; SEM] years) men had one leg immobilized for 2 weeks, followed by 6 weeks' bicycle endurance retraining. Maximal voluntary contraction, leg work capacity (Wmax), and leg lean mass by dual energy X-ray absorptiometry were measured at inclusion, after immobilization and after 3 and 6 weeks' retraining. Muscle biopsies were evaluated for fibre type, fibre area, and capillarization.

See full abstract

Vigelsø A, Gram M, Wiuff C, Hansen CN, Prats C, Dela F and Helge JW. Effects of immobilization and aerobic training on proteins related to intramuscular substrate and metabolism in young and older men. European Journal of Applied Physiology. Accepted, 2015. 

Abstract

Aging and inactivity lead to skeletal muscle metabolic inflexibility, but the underlying molecular mechanisms are not entirely elucidated. Therefore, we investigated how muscle lipid and glycogen stores and major regulatory proteins were affected by short-term immobilization followed by aerobic training in young andolder men. 17 young (23 ± 1 years, 24 ± 1 kg m(-2), and 20 ± 2 % body fat) and 15 older men (68 ± 1 years; 27 ± 1 kg m(-2), and 29 ± 2 % body fat) underwent 2 weeks' one leg immobilization followed by 6 weeks' cycletraining. Biopsies were obtained from m. vastus lateralis just before immobilization (at inclusion), afterimmobilization, and the after 6 weeks' training. The biopsies were analyzed for muscle substrates; muscle perilipin protein (PLIN), glycogen synthase (GS), synaptosomal-associated protein of 23 kDa (SNAP23) protein content, and muscle 3-hydroxyacyl-CoA dehydrogenase (HAD) activity

See full abstract

Vigelso A, Prats C, Ploug T, Dela F and Helge JW. Higher muscle content of perilipin 5 and endothelial lipase protein in trained than untrained middle-aged men. Physiological Research. Accepted, 2015.

Abstract

A high VO(2)max in middle-age is related to high metabolic flexibility and lowered risk of metabolic diseases. However, the influence of a high VO(2)max induced by years of regular training in middle-age on proteinexpression related to muscle metabolism is not well studied. This study measures key proteins involved in mitochondrial oxidation, glucose and lipid metabolism in skeletal muscle of trained and untrained middle-agedmen. 16 middle-aged men, matched for lean body mass, were recruited into an endurance trained (TR, n=8) or an untrained (CON, n=8) group based on their VO(2)max. A muscle biopsy was obtained from m. vastus lateralis and protein levels were analysed by Western blotting. 

See full abstract

Waller KL, Mortensen EL, Avlund K, Osler M, Fagerlund B, Lauritzen M and Jennum P. Subjective sleep quality and daytime sleepiness in late midlife and their association with age-related changes in cognition. Sleep Medicine. Accepted, 2015.

Abstract

In an increasingly aged population, sleep disturbances and neurodegenerative disorders have become a major public health concern. Poor sleep quality and cognitive changes are complex health problems in aging populations that are likely to be associated with increased frailty, morbidity, and mortality, and to be potential risk factors for further cognitive impairment. We aimed to evaluate whether sleep quality and excessivedaytime sleepiness may be considered as early predictors of cognitive impairment. The objective of this study was to examine whether subjective sleep quality anddaytime sleepiness are associated with cognition in middle-aged males. A total of 189 healthy males born in 1953 were considered as participants for the study. Based on previous cognitive assessments, the participants were selected for the study as cognitively improved (N = 97) or cognitively impaired (N = 92). The Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale measured subjective sleepquality and daytime sleepiness, respectively. Depressive symptoms were determined using Beck's Depression Inventory (BDI-II). A neuropsychological battery was administered to confirm group differences in cognitive functioning at the time when sleep data were collected.

See full abstract

Wimmelmann CL, Smith E, Lund MT,  Dela F and Mortensen EL. The psychological profile of bariatric patients with and without type 2 diabetes: Baseline results of the longitudinal GASMITO-PSYC study. Surgery for Obesity and Related Diseases. 11: 412-418, 2015.

Abstract

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

See full abstract

Ziegler AK, Grand J, Stangerup I, Nielsen, HJ, Dela F, Magnussen K and Helge JW. Time course for the recovery of physical performance, blood hemoglobin, and ferritin content after blood donation. Transfusion.  55: 898-905, 2015.

Abstract

It is widely accepted that blood donation negatively affects endurance performance, but data on physical recovery after a standard blood donation are scarce. This study aimed to elucidate the temporary impact of blood donation on endurance performance, measured as peak oxygen uptake (VO2peak ) and timetrial (TT) performance. VO2peak , TT performance, blood, iron, and anthropometric variables were determined before (baseline) and 3, 7, 14, and 28 days after blood donation in 19 healthy men.

See full abstract

Theme 3Til toppen

Agergaard J, Trøstrup J, Uth J, Iversen JV, Boesen A, Andersen JL, Schjerling P and Langberg H. Does vitamin-D intake during resistance training improve the skeletal muscle hypertrophic and strength response in young and elderly men? - a randomized controlled trial. Nutrition & Metabolism. 12:32, 2015.

Abstract

Recent studies have shown that vitamin-D intake can improve skeletal muscle function andstrength in frail vitamin-D insufficient individuals. We investigated whether vitamin-D intake can improve the muscular response to resistance training in healthy young and elderly individuals, respectively. Healthy untrained young (n = 20, age 20-30) and elderly (n = 20, age 60-75) men were randomizedto 16 weeks of daily supplementary intake of either 48 μg of vitamin-D + 800 mg calcium (Vitamin-D-group) or 800 mg calcium (Placebo-group) during a period and at a latitude of low sunlight (December-April, 56°N). During the last 12 weeks of the supplementation the subjects underwent progressive resistance training of the quadriceps muscle. Muscle hypertrophy, measured as changes in cross sectional area (CSA), and isometricstrength of the quadriceps were determined. Muscle biopsies were analyzed for fiber type morphology changes and mRNA expression of vitamin-D receptor (VDR), cytochrome p450 27B1 (CYP27B1) and Myostatin.

See full abstract

Beyer R, Kongsgaard M, Kjaer BH, Ohlenschlaeger T, Kjaer M and Magnusson SP. Heavy slow resistance versus eccentric training as a treatment of Achilles tendinopathy: A randomized controlled trial. Am J Sports Med. 43: 1704-11, 2015.

Abstract

Previous studies have shown that eccentric training has a positive effect on Achillestendinopathy, but few randomized controlled trials have compared it with other loading-based treatmentregimens. To evaluate the effectiveness of eccentric training (ECC) and heavy slow resistance training(HSR) among patients with midportion Achilles tendinopathy. Randomized controlled trial; Level of evidence, 1. A total of 58 patients with chronic (>3 months) midportion Achilles tendinopathy were randomizedto ECC or HSR for 12 weeks. Function and symptoms (Victorian Institute of Sports Assessment-Achilles), tendon pain during activity (visual analog scale), tendon swelling, tendon neovascularization, and treatmentsatisfaction were assessed at 0 and 12 weeks and at the 52-week follow-up. Analyses were performed on an intention-to-treat basis.

See full abstract

Brandt N, O'Neill HM, Kleinert M, Schjerling P, Vernet E, Steinberg GR, Richter EA and Jørgensen SB. Leukemia inhibitory factor increases glucose uptake in mouse skeletal muscle. American Journal of Physiology. 309: E142-53, 2015.

Members of the IL-6 family, IL-6 and ciliary neurotrophic factor (CNTF), have been shown to increase glucoseuptake and fatty acid oxidation in skeletal muscle. However, the metabolic effects of another family member,leukemia inhibitory factor (LIF), are not well characterized. Effects of LIF on skeletal muscle glucose uptakeand palmitate oxidation and signaling were investigated in ex vivo incubated mouse soleus and EDL muscles from muscle-specific AMPKα2 kinase-dead, muscle-specific SOCS3 knockout, and lean and high-fat-fed mice. Inhibitors were used to investigate involvement of specific signaling pathways. LIF increased muscleglucose uptake in dose (50-5,000 pM/l) and time-dependent manners with maximal effects at the 30-min time point. LIF increased Akt Ser(473) phosphorylation (P) in soleus and EDL, whereas AMPK Thr(172) P was unaffected. 

See full abstract

Bursomanno S, Beli P, Khan AM, Minocherhomji S, Wagner SA, Bekker-Jensen S, Mailand N, Choudhary C, Hickson ID and Liu Y. Proteome-wide analysis of SUMO2 targets in response to pathological DNA replication stress in human cells. DNA Repair. 25: 84-96, 2015.

Abstract

SUMOylation is a form of post-translational modification involving covalent attachment of SUMO (Small Ubiquitin-like Modifier) polypeptides to specific lysine residues in the target protein. In human cells, there are four SUMO proteins, SUMO1-4, with SUMO2 and SUMO3 forming a closely related subfamily. SUMO2/3, in contrast to SUMO1, are predominantly involved in the cellular response to certain stresses, including heat shock. Substantial evidence from studies in yeast has shown that SUMOylation plays an important role in the regulation of DNA replication and repair. Here, we report a proteomic analysis of proteins modified by SUMO2in response to DNA replication stress in S phase in human cells. We have identified a panel of 22 SUMO2targets with increased SUMOylation during DNA replication stress, many of which play key functions within the DNA replication machinery and/or in the cellular response to DNA damage.

See full abstract

Bursomanno S, McGouran JF, Kessler BM, Hickson ID and Liu Y. Regulation of SUMO2 Target Proteins by the Proteasome in Human Cells Exposed to Replication Stress. J Proteome Res. 14: 1687-1699, 2015.

Abstract

In human cells, SUMO2 is predominantly conjugated to target proteins in response to cellular stress. Previous studies suggested that proteins conjugated to SUMO2, but not to SUMO1, could be regulated by the ubiquitin-mediated proteasome system. Hence, we set out to understand the role of the proteasome in determining the fate of proteins conjugated to SUMO2 when cells are treated with DNA replication stress conditions. We conducted a quantitative proteomic analysis in a U2OS cell line stably expressing SUMO2(Q87R) tagged with StrepHA in the presence or absence of epoxomicin (EPOX), a proteasome inhibitor. We identified subgroups of putative SUMO2 targets that were either degraded or stabilized by EPOX upon SUMO2 conjugation in response to replication stress. Interestingly, the subgroup of proteins degraded upon SUMO2 conjugation was enriched in proteins playing roles in DNA damage repair and replication, while the proteins stabilized upon SUMOylation were mainly involved in chromatin maintenance. In addition, we identified 43 SUMOylation sites in target proteins, of which 17 are located in the proximity of phosphorylated residues. Considering that DNAreplication stress is a major source of genome instability, which is suggested to drive tumorigenesis and possibly aging, our data will facilitate future functional studies in the fields of DNA metabolism and cancer biology.

See full abstract

Chu WK, Payne MJ, Beli P, Hanada K, Choudhary C and Hickson ID. FBH1 influences DNA replication fork stability and homologous recombination through ubiquitylation of RAD51. Nature Communications. 6: 5931, 2015. 

Abstract

Unscheduled homologous recombination (HR) can lead to genomic instability, which greatly increases the threat of neoplastic transformation in humans. The F-box DNA helicase 1 (FBH1) is a 3'-5' DNA helicase with a putative function as a negative regulator of HR. It is the only known DNA helicase to contain an F-box, suggesting that one of its functions is to act as a ubiquitin ligase as part of an SCF (SKP1, CUL1 and F-box) complex. Here we report that the central player in HR, RAD51, is ubiquitylated by the SCF(FBH1) complex. Expression of an ubiquitylation-resistant form of RAD51 in human cells leads to hyperrecombination, as well as several phenotypes indicative of an altered response to DNA replication stress. These effects are likely to be mediated by the enhanced nuclear matrix association of the ubiquitylation-resistant RAD51. These data are consistent with FBH1 acting as a negative regulator of RAD51 function in human cells.

See full abstract

Couppé C, Svensson RB, Kongsgaard M, Kovanen V, Grosset JF, Snorgaard O, Bencke J, Larsen JO, Bandholm T, Christensen TM, Boesen A, Helmark IC, Aagaard P, Kjær M and Magnusson SP. Human Achilles tendon glycation and function in diabetes. Journal of Applied Physiology. Accepted, 2015.

Abstract

Diabetic patients have an increased risk of foot ulcers, and glycation of collagen may increase tissue stiffness. We hypothesized that the level of glycemic control (glycation) may affect Achilles tendon stiffness, which can influence gait pattern. We therefore investigated the relationship between collagen glycation,Achilles tendon stiffness parameters, and plantar pressure in poorly (n = 22) and well (n = 22) controlled diabetic patients, including healthy age-matched (45-70 yr) controls (n = 11). There were no differences in any of the outcome parameters (collagen cross-linking or tendon stiffness) between patients with well-controlled and poorly controlled diabetes. The overall effect of diabetes was explored by collapsing the diabetes groups (DB) compared with the controls. Skin collagen cross-linking lysylpyridinoline, hydroxylysylpyridinoline (136%, 80%, P < 0.01) and pentosidine concentrations (55%, P < 0.05) were markedly greater in DB.

See full abstract

Couppé C, Svensson RB, Silbernagel KG, Langberg H and Magnusson SP. The Influence of Exercise Load in the Treatment of Tendinopathies. Journal of Orthopedic and Sports Physical Therapy. 45: 853-863, 2015.

Desler C, Frederiksen JH, Angleys M, Maynard S, Keijzers G, Fagerlund B, Mortensen EL, Osler M, Lauritzen M, Bohr VA and Rasmussen LJ. Increased deoxythymidine triphosphate levels is a feature of relative cognitive decline. Mitochondrion. 25: 34-37, 2015.

Abstract

Mitochondrial bioenergetics, mitochondrial reactive oxygen species (ROS) and cellular levels of nucleotides have been hypothesized as early indicators of Alzheimer's disease (AD). Utilizing relative decline of cognitiveability as a predictor of AD risk, we evaluated the correlation between change of cognitive ability and mitochondrial bioenergetics, ROS and cellular levels of deoxyribonucleotides. Change of cognitive abilities, scored at ages of approximately 20 and 57 was determined for a cohort of 1985 male participants. Mitochondrial bioenergetics, mitochondrial ROS and whole-cell levels of deoxyribonucleotide triphosphates were measured in peripheral blood mononuclear cells (PBMCs) from a total of 103 selected participants displaying the most pronounced relative cognitive decline and relative cognitive improvement. 

See full abstract

Fentz J, Kjøbsted R, Birk JB, Jordy AB, Jeppesen J, Thorsen K, Schjerling P, Kiens B, Jessen N, Viollet B and Wojtaszewski JF. AMPKα is critical for enhancing skeletal muscle fatty acid utilization during in vivo exercise in mice. FASEB Journal. 29: 1725-38, 2015.

Abstract

The importance of AMPK in regulation of fatty acid (FA) oxidation in skeletal muscle with contraction/exerciseis unresolved. Using a mouse model lacking both AMPKα1 and -α2 in skeletal muscle specifically (mdKO), we hypothesized that FA utilization would be impaired in skeletal muscle. AMPKα mdKO mice displayed normal respiratory exchange ratio (RER) when fed chow or a high-fat diet, or with prolonged fasting. However, in vivo treadmill exercise at the same relative intensity induced a higher RER in AMPKα mdKO micecompared to wild-type (WT = 0.81 ± 0.01 (sem); mdKO = 0.87 ± 0.02 (sem); P < 0.01), indicating a decreasedutilization of FA. Further, ex vivo contraction-induced FA oxidation was impaired in AMPKα mdKO muscle, suggesting that the increased RER during exercise originated from decreased skeletal muscle FA oxidation.

See full abstract

Fentz J, Kjøbsted R, Kristensen CM, Hingst JR, Birk JB, Gudiksen A, Foretz M, Schjerling P, Viollet B, Pilegaard H and Wojtaszewski JF. AMPKα is essential for acute exercise-induced gene responses but not for exercise training-induced adaptations in mouse skeletal muscle. American Journal of Physiology. 309: E900-14, 2015.

Abstract

Exercise training increases skeletal muscle expression of metabolic proteins improving the oxidative capacity.Adaptations in skeletal muscle by pharmacologically induced activation of 5'-AMP-activated protein kinase (AMPK) are dependent on the AMPKα2 subunit. We hypothesized that exercise training-induced increases inexercise capacity and expression of metabolic proteins, as well as acute exercise-induced gene regulation, would be compromised in muscle-specific AMPKα1 and -α2 double-knockout (mdKO) mice. An acute bout ofexercise increased skeletal muscle mRNA content of cytochrome c oxidase subunit I, glucose transporter 4, and VEGF in an AMPK-dependent manner, whereas cluster of differentiation 36 and fatty acid transport protein 1 mRNA content increased similarly in AMPKα wild-type (WT) and mdKO mice. During 4 wk of voluntary running wheel exercise training, the AMPKα mdKO mice ran less than WT. 

See full abstract

Fugger K, Mistrik M, Neelsen KJ, Yao Q, Zellweger R, Kousholt AN, Haahr P, Chu WK, Bartek J, Lopes M, Hickson ID and Sørensen CS. FBH1 Catalyzes Regression of Stalled Replication Forks. Cell Reports. 10: 1749-1757, 2015.

Abstract

DNA replication fork perturbation is a major challenge to the maintenance of genome integrity. It has been suggested that processing of stalled forks might involve fork regression, in which the fork reverses and the two nascent DNA strands anneal. Here, we show that FBH1 catalyzes regression of a model replication fork in vitro and promotes fork regression in vivo in response to replication perturbation. Cells respond to fork stalling by activating checkpoint responses requiring signaling through stress-activated protein kinases. Importantly, we show that FBH1, through its helicase activity, is required for early phosphorylation of ATM substrates such as CHK2 and CtIP as well as hyperphosphorylation of RPA.

See full abstract

Herchenhan A, Bayer ML, Eliasson P, Magnusson SP and Kjaer M. Insulin-like growth factor I enhances collagen synthesis in engineered human tendon tissue. Growth Horm IGF Res. 25: 13-19, 2015.

Abstract

Isolated human tendon cells form 3D tendon constructs that demonstrate collagenfibrillogenesis and feature structural similarities to tendon when cultured under tensile load. The exact role of circulating growth factors for collagen formation in tendon is sparsely examined. We investigated the influence of insulin-like growth factor I (IGF-I) on tendon construct formation in 3D cell culture. Tendon constructs were grown in 0.5 or 10% FBS with or without IGF-I (250 mg/ml) supplementation. Collagen content (fluorometric), mRNA levels (PCR) and fibril diameter (transmission electron microscopy) were determined at 7, 10, 14, 21 and 28 days.

See full abstract

Hershenhan A, Uhlenbrock F, Eliasson P, Weis M-A, Eyre D, Kadler KE, Magnusson SP and Kjaer M. Lysyl Oxidase activity is required for ordered collagen fibrillogenesis by tendon cells. J Biol Chem. 290: 16440-50, 2015.

Abstract

Lysyl oxidases (LOXs) are a family of copper-dependent oxido-deaminases that can modify the side chain oflysyl residues in collagen and elastin, thereby leading to the spontaneous formation of non-reducible aldehyde-derived interpolypeptide chain cross-links. The consequences of LOX inhibition in producing lathyrism are well documented, but the consequences on collagen fibril formation are less clear. Here we used β-aminoproprionitrile (BAPN) to inhibit LOX in tendon-like constructs (prepared from human tenocytes), which are an experimental model of cell-mediated collagen fibril formation. The improvement in structure and strength seen with time in control constructs was absent in constructs treated with BAPN. As expected, BAPN inhibited the formation of aldimine-derived cross-links in collagen, and the constructs were mechanically weak. However, an unexpected finding was that BAPN treatment led to structurally abnormalcollagen fibrils with irregular profiles and widely dispersed diameters.

See full abstract

Holm C, Kjaer M and Eliasson P. Achilles tendon rupture – treatment and complications: A systematic review. Scand J Med Sci Sports. 25: e1-10, 2015.

Abstract

Achilles tendon rupture is a frequent injury with an increasing incidence. Until now, there is no consensus regarding optimal treatment. The aim of this review was to illuminate and summarize randomized controlled trials comparing surgical and non-surgical treatment of Achilles tendon ruptures during the last 10 years. Seven articles were found and they were all acceptable according to international quality assessment guidelines. Primary outcomes were re-ruptures, other complications, and functional outcomes. There was no significant difference in re-ruptures between the two treatments, but a tendency to favouring surgical treatment. Further, one study found an increased risk of soft-tissue-related complications after surgery. Patient satisfaction and time to return to work were significantly different in favour of surgery in one study, and there was also better functional outcome after surgery in some studies. These seven studies indicate that surgical patients have a faster rehabilitation. 

See full abstract

Holm L, Jespersen AP, Nielsen DS, Frøst MB, Reitelseder S, Jensen T, Engelsen SB, Kjaer M, Damsholt T. Hurrah for the increasing longevity: Feasible strategies to counteract age-related loss of skeletal muscle mass. Scand J Med Sci Sports. 25: 1-2, 2015.

Joyner M, Kjaer M and Larsen PO. The Copenhagen Muscle Research Centre (CMRC) 1994-2004. Scand J Med Sci Sports. 25 (4): 22-28, 2015.

Abstract

This paper presents an impressionistic summary of the formation, activities, accomplishments, and impact of the Copenhagen Muscle Research Centre (CMRC) from 1994 to 2004. The history of the CMRC is viewed in the context of the goals of the original program, the tradition of excellence in exercise physiology in Copenhagen since the time of August Krogh, and the structure of the center. The key role of Professor Bengt Saltin as a visionary, flexible, and inclusive leader is highlighted.

See full abstract

Karlsen A, Couppé C, Andersen JL, Mikkelsen UR, Nielsen RH, Magnusson P, Kjaer M and Mackey AL. Matters of fiber size and myonuclear domain; does size matter more than age? Muscle Nerve. 52: 1040-1046, 2015.

Abstract

The relationship between fiber size and myonuclear content is poorly understood. Biopsy cross-sections from young and old trained and untrained healthy individuals were analyzed for fiber area and myonuclei, and 2 fiber-size-dependent cluster analyses were performed.

See full abstract

Keijzers G, Bohr VA and Rasmussen LJ. Human exonuclease 1 (EXO1) activity characterization and its function on FLAP structures. Biosci Rep. 25: 35(3). 2015.

Abstract

Human exonuclease 1 (EXO1) is involved in multiple DNA metabolism processes, including DNA repair and replication. Most of the fundamental roles of EXO1 have been described in yeast. Here, we report a biochemical characterization of human full-length EXO1. Prior to assay EXO1 on different DNA flapstructures, we determined factors essential for the thermodynamic stability of EXO1. We show that enzymaticactivity and stability of EXO1 on DNA is modulated by temperature. By characterization of EXO1 flap activityusing various DNA flap substrates, we show that EXO1 has a strong capacity for degrading double stranded DNA and has a modest endonuclease or 5' flap activity. Furthermore, we report novel mechanistic insights into the processing of flap structures, showing that EXO1 preferentially cleaves one nucleotide inwards in a double stranded region of a forked and nicked DNA flap substrates, suggesting a possible role of EXO1 in strand displacement.

See full abstract

Kjaer M, Jørgensen NR, Heinemeier K and Magnusson SP. Exercise and regulation of bone and collagen tissue biology. Prog Mol Biol Transl Sci. 135: 259-291, 2015.

Abstract

The musculoskeletal system and its connective tissue include the intramuscular connective tissue, the myotendinous junction, the tendon, the joints with their cartilage and ligaments, and the bone; they all together play a crucial role in maintaining the architecture of the skeletal muscle, ensuring force transmission, storing energy, protecting joint surface and stability, and ensuring the transfer of muscular forces into resulting limb movement. The musculoskeletal connective tissue structure is relatively stable, but mechanical loading and subsequent mechanotransduction and molecular anabolic signaling can result in some adaptation of the connective tissue, its size, its strength, and its mechanical properties, whereby it can improve its capacity by 5-20% with regular physical activity.

See full abstract

Kjøbsted R, Treebak JT, Fentz J, Lantier L, Viollet B, Birk JB, Schjerling P, Björnholm M, Zierath JR and Wojtaszewski JF. Prior AICAR stimulation increases insulin sensitivity in mouse skeletal muscle in an AMPK-dependent manner. Diabetes. 64: 2042-55, 2015.

Abstract

An acute bout of exercise increases glucose uptake in skeletal muscle by an insulin-independent mechanism. In the period after exercise, insulin sensitivity to increased glucose uptake is enhanced. The molecular mechanisms underpinning this phenomenon are poorly understood but appear to involve an increased cell surface abundance of GLUT4. While increased proximal insulin signaling does not seem to mediate this effect, elevated phosphorylation of TBC1D4, a downstream target of both insulin (Akt) and exercise (AMPK) signaling, appears to play a role. The main purpose of this study was to determine whether AMPK activationincreases skeletal muscle insulin sensitivity. We found that prior AICAR stimulation of wild-type mousemuscle increases insulin sensitivity to stimulate glucose uptake. However, this was not observed in mice with reduced or ablated AMPK activity in skeletal muscle.

See full abstract

Kliszczak M, Sedlackova H, Pitchai GP, Streicher WW, Krejci L and Hickson ID. Interaction of RECQ4 and MCM10 is important for efficient DNA replication origin firing in human cells. Oncotarget. 6: 40464-40479, 2015.

Abstract

DNA replication is a highly coordinated process that is initiated at multiple replication origins in eukaryotes. These origins are bound by the origin recognition complex (ORC), which subsequently recruits the Mcm2-7 replicative helicase in a Cdt1/Cdc6-dependent manner. In budding yeast, two essential replication factors, Sld2 and Mcm10, are then important for the activation of replication origins. In humans, the putative Sld2 homolog, RECQ4, interacts with MCM10. Here, we have identified two mutants of human RECQ4 that are deficient in binding to MCM10. We show that these RECQ4 variants are able to complement the lethality of an avian cell RECQ4 deletion mutant, indicating that the essential function of RECQ4 in vertebrates is unlikely to require binding to MCM10. Nevertheless, we show that the RECQ4-MCM10 interaction is important forefficient replication origin firing.

See full abstract

Knudsen AB, Larsen M, Mackey AL, Hjort M, Hansen KK, Qvortrup K and Kjaer M and Krogsgaard MR. The human myotendinous junction: An ultrastructural and a 3D analysis study. Scand J Med Sci Sports. 25: e116-23, 2015.

Abstract

The myotendinous junction (MTJ) is a specialized structure in the musculotendinous system, where force is transmitted from muscle to tendon. Animal models have shown that the MTJ takes form of tendon finger-like processes merging with muscle tissue. The human MTJ is largely unknown and has never been described in three dimensions (3D). The aim of this study was to describe the ultrastructure of the human MTJ and render3D reconstructions. Fourteen subjects (age 25 ± 3 years) with isolated injury of the anterior cruciate ligament (ACL), scheduled for reconstruction with a semitendinosus/gracilis graft were included. Semitendinosus and gracilis tendons were stripped as grafts for the ACL reconstruction.

See full abstract

Kvorning T, Kadi F, Schjerling P, Andersen M, Brixen K, Suetta C and Madsen K. The activity of satellite cells and myonuclei following 8 weeks of strength training in young men with suppressed testosterone levels. Acta Physiology. 213: 676-87, 2015.

Abstract

To investigate how suppression of endogenous testosterone during an 8-week strength training period influences the activity of satellite cells and myonuclei.Twenty-two moderately trained young men participated in this randomized, placebo-controlled, and double-blinded intervention study. The participants were randomized to treatment with a GnRH analogue, goserelin (n = 12), which suppresses testosterone or placebo (n = 10) for 12 weeks. The strength trainingperiod of 8 weeks started after 4 weeks of treatment and included exercises for all major muscles. Biopsies were obtained from the mid-portion of the vastus lateralis muscle.

See full abstract

Lauritzen KH, Kleppa L, Aronsen JM, Eide L, Carlsen H, Haugen ØP, Sjaastad I, Klungland A, Rasmussen LJ, Attramadal H, Storm-Mathisen J and Bergersen LH. Impaired dynamics and function of mitochondria caused by mtDNA toxicity leads to heart failure. Am J Physiol Heart Circ Physiol. 309: H434-49, 2015.

Abstract

Cardiac mitochondrial dysfunction has been implicated in heart failure of diverse etiologies. Generalized mitochondrial disease also leads to cardiomyopathy with various clinical manifestations. Impairedmitochondrial homeostasis may over time, such as in the aging heart, lead to cardiac dysfunction. Mitochondrial DNA (mtDNA), close to the electron transport chain and unprotected by histones, may be a primary pathogenetic site, but this is not known. Here, we test the hypothesis that cumulative damage of cardiomyocyte mtDNA leads to cardiomyopathy and heart failure. Transgenic mice with Tet-on inducible, cardiomyocyte-specific expression of a mutant uracil-DNA glycosylase 1 (mutUNG1) were generated. The mutUNG1 is known to remove thymine in addition to uracil from the mitochondrial genome, generating apyrimidinic sites, which obstruct mtDNA function.

See full abstract

Lenskjold A, Kongsgaard M, Larsen JO, Nielsen RH, Kovanen V, Aagaard P, Kjaer M and Magnusson SP. The influence of physical activity during youth on structural and functional properties of the Achilles tendon. Scand J Med Sci Sports. 25: 25-31, 2015.

Abstract

Achilles tendinopathy is a highly prevalent sports injury. Animal studies show a growth response in tendons in response to loading in the immature phase but not after puberty maturation. The aim of this investigation was to examine the structural and material properties in long distance runners who were either physically active (HAY) or inactive (LAY) in young age. Twelve men in HAY group and eight men in LAY group participated.Structural, functional, and biochemical properties of Achilles tendon were estimated from magnetic resonance imaging, ultrasound video recordings, mechanical tests, and tendon biopsies, respectively. 

See full abstract

Lopez-Contreras AJ, Specks J, Barlow JH, Ambrogio C, Desler C, Vikingsson S, Rodrigo-Perez S, Green H, Rasmussen LJ, Murga M, Nussenzweig A and Fernandez-Capetillo O. Increased Rrm2 gene dosage reduces fragile site breakage and prolongs survival of ATR mutant mice. Genes & Dev. 29: 690-695, 2015.

Abstract

In Saccharomyces cerevisiae, absence of the checkpoint kinase Mec1 (ATR) is viable upon mutations that increase the activity of the ribonucleotide reductase (RNR) complex. Whether this pathway is conserved in mammals remains unknown. Here we show that cells from mice carrying extra alleles of the RNR regulatory subunit RRM2 (Rrm2(TG)) present supraphysiological RNR activity and reduced chromosomal breakage atfragile sites. Moreover, increased Rrm2 gene dosage significantly extends the life span of ATR mutant mice. Our study reveals the first genetic condition in mammals that reduces fragile site expression and alleviates the severity of a progeroid disease by increasing RNR activity.

See full abstract

Mansour A, Marya M, Deborah C and Bohr VA. The role of DNA base excision repair in brain homeostasis and disease. DNA Repair. 32: 172-9, 2015.

Abstract

Chemical modification and spontaneous loss of nucleotide bases from DNA are estimated to occur at the rate of thousands per human cell per day. DNA base excision repair (BER) is a critical mechanism for repairing such lesions in nuclear and mitochondrial DNA. Defective expression or function of proteins required for BER or proteins that regulate BER have been consistently associated with neurological dysfunction and disease in humans. 

See full abstract

Mansour A, Peter S and Bohr VA. Slow mitochondrial repair of 5′-AMP renders mtDNA susceptible to damage in APTX deficient cells. Scientific Reports. 10(5): 12876, 2015.

Abstract

Aborted DNA ligation events in eukaryotic cells can generate 5'-adenylated (5'-AMP) DNA termini that can be removed from DNA by aprataxin (APTX). Mutations in APTX cause an inherited human disease syndrome characterized by early-onset progressive ataxia with ocular motor apraxia (AOA1). APTX is found in the nuclei and mitochondria of eukaryotic cells. Depletion of APTX causes mitochondrial dysfunction and renders themitochondrial genome, but not the nuclear genome susceptible to damage. The biochemical processes that link APTX deficiency to mitochondrial dysfunction have not been well elucidated.

See full abstract

Maynard S, Fang EF, Scheibye-Knudsen M, Croteau DL and Bohr VA. DNA Damage, DNA Repair, Aging, and Neurodegeneration. Cold Spring Harb Perspect Med. 18: 5(10), 2015.

Abstract

Aging in mammals is accompanied by a progressive atrophy of tissues and organs, and stochastic damageaccumulation to the macromolecules DNA, RNA, proteins, and lipids. The sequence of the human genome represents our genetic blueprint, and accumulating evidence suggests that loss of genomic maintenance may causally contribute to aging. Distinct evidence for a role of imperfect DNA repair in aging is that several premature aging syndromes have underlying genetic DNA repair defects. Accumulation of DNA damage may be particularly prevalent in the central nervous system owing to the low DNA repair capacity in postmitotic brain tissue. It is generally believed that the cumulative effects of the deleterious changes that occur in aging, mostly after the reproductive phase, contribute to species-specific rates of aging. In addition to nuclear DNA damage contributions to aging, there is also abundant evidence for a causative link between mitochondrialDNA damage and the major phenotypes associated with aging. 

See full abstract

Maynard S, Hejl AM, Dinh TST, Keijzers G, Hansen ÅM, Desler C, Moreno-Villanueva M, Bürkle A, Rasmussen LJ, Waldemar G and Bohr VA. Defective mitochondrial respiration, altered dNTP pools and reduced AP endonuclease 1 activity in peripheral blood mononuclear cells of Alzheimer’s disease patients. Aging. 7: 793-815, 2015.

Abstract

Accurate biomarkers for early diagnosis of Alzheimer's disease (AD) are badly needed. Recent reports suggest that dysfunctional mitochondria and DNA damage are associated with AD development. In this report, we measured various cellular parameters, related to mitochondrial bioenergetics and DNA damage, inperipheral blood mononuclear cells (PBMCs) of AD and control participants, for biomarker discovery. PBMCs were isolated from 53 patients with AD of mild to moderate degree and 30 age-matched healthy controls. Tests were performed on the PBMCs from as many of these participants as possible. We measured glycolysis and mitochondrial respiration fluxes using the Seahorse Bioscience flux analyzer,mitochondrial ROS production using flow cytometry, dNTP levels by way of a DNA polymerization assay, DNA strand breaks using the Fluorometric detection of Alkaline DNA Unwinding (FADU) assay, and APE1 incisionactivity (in cell lysates) on a DNA substrate containing an AP site (to estimate DNA repair efficiency).

See full abstract

Maynard S, Keijzers G, Hansen ÅM, Osler M, Molbo D, Bendix L, Møller P, Loft S, Moreno-Villanueva M, Bürkle A, Poulsen Hvitby C, Schurman SH, Stevnsner T, Rasmussen LJ, Avlund K and Bohr VA. Associations of subjective vitality with DNA damage, cardiovascular risk factors and physical performance. Acta Physiologica. 213: 156-170, 2015.

Abstract

To examine associations of DNA damage, cardiovascular risk factors and physical performance withvitality, in middle-aged men. We also sought to elucidate underlying factors of physical performance by comparing physical performance parameters to DNA damage parameters and cardiovascular risk factors. We studied 2487 participants from the Metropolit cohort of 11 532 men born in 1953 in the Copenhagen Metropolitan area. The vitality level was estimated using the SF-36 vitality scale. Cardiovascularrisk factors were determined by body mass index (BMI), and haematological biochemistry tests obtained from non-fasting participants. DNA damage parameters were measured in peripheral blood mononuclear cells (PBMCs) from as many participants as possible from a representative subset of 207 participants.

See full abstract

Mikkelsen UR, Dideriksen K, Andersen MB, Boesen A, Malmgaard-Clausen NM, Sørensen IJ, Schjerling P, Kjaer M and Holm L. Preserved skeletal muscle protein anabolic response to acute exercise and protein intake in well-treated rheumatoid arthritis patients. Arthritis Res Ther. 17: 271-281, 2015.

Abstract

Rheumatoid arthritis (RA) is often associated with diminished muscle mass, reflecting an imbalance between protein synthesis and protein breakdown. To investigate the anabolic potential of bothexercise and nutritional protein intake we investigated the muscle protein synthesis rate and anabolicsignaling response in patients with RA compared to healthy controls. Thirteen RA patients (age range 34-84 years; diagnosed for 1-32 years, median 8 years) were individually matched with 13 healthy controls for gender, age, BMI and activity level (CON). Plasma levels of C-reactive protein (CRP), interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured using enzyme-linked immunosorbent assay (ELISA) in resting blood samples obtained on two separate days. Skeletalmuscle myofibrillar and connective tissue protein fractional synthesis rate (FSR) was measured by incorporation of the amino acid (13)C6-phenylalanine tracer in the overnight fasted state for 3 hours (BASAL) and 3 hours after intake of whey protein (0.5 g/kg lean body mass) alone (PROT, 3 hrs) and in combination with knee-extensor exercise (EX) with one leg (8 × 10 reps at 70 % of 1RM; PROT + EX, 3 hrs). Expression of genes related to inflammatory signaling, myogenesis and muscle growth/atrophy were analyzed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR).

See full abstract

Minocherhomji S, Ying S, Bjerregaard VA, Bursomanno S, Aleliunaite A, Wu W, Mankouri HW, Shen H, Liu Y and Hickson ID. Replication stress activates DNA repair synthesis in mitosis. Nature. 528: 286-290, 2015.

Abstract

Oncogene-induced DNA replication stress has been implicated as a driver of tumorigenesis. Many chromosomal rearrangements characteristic of human cancers originate from specific regions of the genome called common fragile sites (CFSs). CFSs are difficult-to-replicate loci that manifest as gaps or breaks on metaphase chromosomes (termed CFS 'expression'), particularly when cells have been exposed to replicativestress. The MUS81-EME1 structure-specific endonuclease promotes the appearance of chromosome gaps or breaks at CFSs following replicative stress. Here we show that entry of cells into mitotic prophase triggers the recruitment of MUS81 to CFSs. 

See full abstract

Newman JA, Savitsky P, Allerston CK, Bizard AH, Özer Ö, Sarlós K, Liu Y, Pardon E, Steyaert J, Hickson ID and Gileadi O. Crystal structure of the Bloom’s syndrome helicase indicates a role for the HRDC domain in conformational changes. Nucleic Acids Research. 43: 5221-5235, 2015.

Abstract

Bloom's syndrome helicase (BLM) is a member of the RecQ family of DNA helicases, which play key roles in the maintenance of genome integrity in all organism groups. We describe crystal structures of the BLMhelicase domain in complex with DNA and with an antibody fragment, as well as SAXS and domainassociation studies in solution. We show an unexpected nucleotide-dependent interaction of the core helicasedomain with the conserved, poorly characterized HRDC domain. The BLM-DNA complex shows an unusual base-flipping mechanism with unique positioning of the DNA duplex relative to the helicase core domains. Comparison with other crystal structures of RecQ helicases permits the definition of structural transitions underlying ATP-driven helicase action, and the identification of a nucleotide-regulated tunnel that may play arole in interactions with complex DNA substrates.

See full abstract

Nielsen CF, Huttner D, Bizard AH, Hirano S, Li T-N, Palmai-Pallag T, Bjerregaard VA, Liu Y, Nigg EA, Wang LH-H and Hickson ID. PICH promotes sister chromatid disjunction and co-operates with topoisomerase II in mitosis. Nature Communications. 6: 8962, 2015.

Abstract

PICH is a SNF2 family DNA translocase that binds to ultra-fine DNA bridges (UFBs) in mitosis. Numerous roles for PICH have been proposed from protein depletion experiments, but a consensus has failed to emerge. Here, we report that deletion of PICH in avian cells causes chromosome structural abnormalities, and hypersensitivity to an inhibitor of Topoisomerase II (Topo II), ICRF-193. ICRF-193-treated PICH(-/-) cells undergo sister chromatid non-disjunction in anaphase, and frequently abort cytokinesis. PICH co-localizes with Topo IIα on UFBs and at the ribosomal DNA locus, and the timely resolution of both structures depends on the ATPase activity of PICH.

See full abstract

Olsen RH, Couppé C, Dall CH, Monk-Hansen T, Mikkelsen UR, Karlsen A, Høst NB, Magnusson SP and Prescott E. Age-related decline in mitral peak diastolic velocities is unaffected in well trained runners. Scandinavian Cardiovascular Journal. 13: 1-24, 2015.

Abstract

We examined whether diastolic left ventricular function in young and senior lifelong endurancerunners was significantly different from that in sedentary age-matched controls, and whether lifelong endurance running appears to modify the age-related decline in diastolic left ventricular function. The study comprised 17 senior athletes (age: 59-75 years, running distance: 30-70 km/week), 10 young athletes (age: 20-36 years, matched for running distance), and 11 senior and 12 young weight-matched sedentary controls. Peak early (E) and late (A) mitral inflow and early (e') and late (a') diastolic and systolic (s') annular longitudinal tissue Doppler velocities were measured by echocardiography during four stages (rest, supine bike exercise at 30% and 60% of maximal workload, and recovery).

See full abstract

Pena-Diaz J and Rasmussen LJ. Approaches to diagnose DNA mismatch repair (MMR) gene defects in cancer. DNA Repair. In press, 2015.

Abstract

The DNA repair pathway mismatch repair (MMR) is responsible for the recognition and correction of DNAbiosynthetic errors caused by inaccurate nucleotide incorporation during replication. Faulty MMR leads to failure to address the mispairs or insertion deletion loops (IDLs) left behind by the replicative polymerases and results in increased mutation load at the genome. The realization that defective MMR leads to a hypermutation phenotype and increased risk of tumorigenesis highlights the relevance of this pathway for human disease. The association of MMR defects with increased risk of cancer development was first observed in colorectal cancer patients that carried inactivating germline mutations in MMR genes and the disease was named as hereditary non-polyposis colorectal cancer (HNPCC). Currently, a growing list of cancers is found to be MMR defective and HNPCC has been renamed Lynch syndrome (LS) partly to include the associated risk of developing extra-colonic cancers.

See full abstract

Ramos-Molina B, López-Contreras AJ, Lambertos A, Dardonville C, Cremades A and Peñafiel R. Influence of ornithine decarboxylase antizymes and antizyme inhibitors on agmatine uptake by mammalian cells. Amino Acids. 47(5): 1025-34, 2015.

Abstract

Agmatine (4-aminobutylguanidine), a dicationic molecule at physiological pH, exerts relevant modulatory actions at many different molecular target sites in mammalian cells, having been suggested that the administration of this compound may have therapeutic interest. Several plasma membrane transporters have been implicated in agmatine uptake by mammalian cells. Here we report that in kidney-derived COS-7 cell line, at physiological agmatine levels, the general polyamine transporter participates in the plasma membrane translocation of agmatine, with an apparent Km of 44 ± 7 µM and Vmax of 17.3 ± 3.3 nmol h(-1) mg(-1) protein, but that at elevated concentrations, agmatine can be also taken up by other transport systems. In the first case, the physiological polyamines (putrescine, spermidine and spermine), several diguanidines and bis(2-aminoimidazolines) and the polyamine transport inhibitor AMXT-1501 markedly decreased agmatineuptake. 

See full abstract

Ruiz S, Lopez-Contreras AJ, Gabut M, Marion RM, Gutierrez-Martinez P, Bua S, Ramirez O, Olalde I, Rodrigo-Perez S, Li H, Marques-Bonet T, Serrano M, Blasco MA, Batada NN and Fernandez-Capetillo O. Limiting replication stress during somatic cell reprogramming reduces genomic instability in induced pluripotent stem cells. Nat Commun. 21(6): 8036, 2015.

Abstract

The generation of induced pluripotent stem cells (iPSC) from adult somatic cells is one of the most remarkable discoveries in recent decades. However, several works have reported evidence of genomicinstability in iPSC, raising concerns on their biomedical use. The reasons behind the genomic instabilityobserved in iPSC remain mostly unknown. Here we show that, similar to the phenomenon of oncogene-induced replication stress, the expression of reprogramming factors induces replication stress. Increasing the levels of the checkpoint kinase 1 (CHK1) reduces reprogramming-induced replication stress and increases the efficiency of iPSC generation. 

See full abstract

Schwartz S, Magnusson SP and McHugh M. Effects of Contract-Relax versus Static Stretching on Length-Tension Relationship. Scandinavian Journal of Medicine & Science in Sports. 25(6): 764-9 2015.

Seynnes OR, Bojsen-Møller J, Albracht K, Arndt A, Cronin NJ, Finni T and Magnusson SP. Ultrasound-based testing of tendon mechanical properties: A critical evaluation. Journal of Applied Physiology. 118: 133-141, 2015.

Abstract

In the past 20 years, the use of ultrasound-based methods has become a standard approach to measuretendon mechanical properties in vivo. Yet the multitude of methodological approaches adopted by various research groups probably contribute to the large variability of reported values. The technique of obtaining and relating tendon deformation to tensile force in vivo has been applied differently, depending on practical constraints or scientific points of view. Divergence can be seen in 1) methodological considerations, such as the choice of anatomical features to scan and to track, force measurements, or signal synchronization; and 2) in physiological considerations related to the viscoelastic behavior or length measurements of tendons. 

See full abstract

Specks J, Lecona E, Lopez-Contreras AJ and Fernandez-Capetillo O. A Single Conserved Residue Mediates Binding of the Ribonucleotide Reductase Catalytic Subunit RRM1 to RRM2 and Is Essential for Mouse Development. Mol Cell Biol. 35(17): 2910-7, 2015.

Abstract

The ribonucleotide reductase (RNR) complex, composed of a catalytic subunit (RRM1) and a regulatorysubunit (RRM2), is thought to be a rate-limiting enzymatic complex for the production of nucleotides. In humans, the Rrm1 gene lies at 11p15.5, a tumor suppressor region, and RRM1 expression in cancer has been shown to predict responses to chemotherapy. Nevertheless, whether RRM1 is essential in mammalian cells and what the effects of its haploinsufficiency are remain unknown. To model RNR function in mice we used a mutation previously described in Saccharomyces cerevisiae (Rnr1-W688G) which, despite being viable, leads to increased interaction of the RNR complex with its allosteric inhibitor Sml1.

See full abstract

Volper BD, Huynh RT, Arthur KA, Noone J, Gordon BD, Zacherle EW, Munoz E, Sorensen MA, Broderick TL, Magnusson SP, Howden R, Hale TM and Carroll CC. The influence of acute and chronic streptozotocin-induced diabetes on rat tendon extracellular matrix and mechanical properties. American Journal of Physiology. 309: R1135-43, 2015.

Abstract

Diabetes is a major risk factor for tendinopathy, and tendon abnormalities are common in diabetic patients. The purpose of the present study was to evaluate the effect of streptozotocin (60 mg/kg)-induced diabetesand insulin therapy on tendon mechanical and cellular properties. Sprague-Dawley rats (n = 40) were divided into the following four groups: nondiabetic (control), 1 wk of diabetes (acute), 10 wk of diabetes (chronic), and 10 wk of diabetes with insulin treatment (insulin). After 10 wk, Achilles tendon and tail fascicle mechanicalproperties were similar between groups (P > 0.05). Cell density in the Achilles tendon was greater in thechronic group compared with the control and acute groups (control group: 7.8 ± 0.5 cells/100 μm(2), acutegroup: 8.3 ± 0.4 cells/100 μm(2), chronic group: 10.9 ± 0.9 cells/100 μm(2), and insulin group: 9.2 ± 0.8 cells/100 μm(2), P < 0.05). The density of proliferating cells in the Achilles tendon was greater in the chronicgroup compared with all other groups (control group: 0.025 ± 0.009 cells/100 μm(2), acute group: 0.019 ± 0.005 cells/100 μm(2), chronic group: 0.067 ± 0.015, and insulin group: 0.004 ± 0.004 cells/100 μm(2), P < 0.05). Patellar tendon collagen content was ∼32% greater in the chronic and acute groups compared with the control or insulin groups (control group: 681 ± 63 μg collagen/mg dry wt, acute group: 938 ± 21 μg collagen/mg dry wt, chronic: 951 ± 52 μg collagen/mg dry wt, and insulin group: 596 ± 84 μg collagen/mg dry wt, P < 0.05). In contrast, patellar tendon hydroxylysyl pyridinoline cross linking and collagen fibril organization were unchanged by diabetes or insulin (P > 0.05). 

See full abstract

Xing M, Wang X, Palmai-Pallag T, Shen H, Helleday T, Hickson ID and Ying S. Acute MUS81 depletion leads to replication fork slowing and a constitutive DNA damage response. Oncotarget. 6: 37638-37646, 2015.

Abstract

The MUS81 protein belongs to a conserved family of DNA structure-specific nucleases that play important roles in DNA replication and repair. Inactivation of the Mus81 gene in mice has no major deleterious consequences for embryonic development, although cancer susceptibility has been reported. We have investigated the role of MUS81 in human cells by acutely depleting the protein using shRNAs. We found thatMUS81 depletion from human fibroblasts leads to accumulation of ssDNA and a constitutive DNA damageresponse that ultimately activates cellular senescence. Moreover, we show that MUS81 is required for efficient replication fork progression during an unperturbed S-phase, and for recovery of productive replicationfollowing replication stalling. These results demonstrate essential roles for the MUS81 nuclease in maintenance of replication fork integrity.

See full abstract

Book chapters:

Bojsen-Moller J and Magnusson SP. Non-uniform loading of the human Achilles tendon in vivo. Exercise and Sports Sciences Reviews. 43: 190-197, 2015.

Helge JW and Kjaer M. Kost, motion og sport, In: Menneskets ernæring. Eds: Astrup A., Bügel S, Dyerberg J, og Stender S. Munksgaard. Kapitel 29, 423-440, 2015.

Kjaer M. Stress loading and matrix remodeling in tendon and skeletal muscle: Cellular mechano-stimulation and tissue remodeling. In: Fascia in Sports and Movement. Ed: Schleip R. Handspring Publ. 39-45, 2015.

Kjær M. Motion og idræt – det hele menneske, Ugeskrift for Læger. 177: 2396, 2015.