The association between childhood motor performance and developmental trajectories of sport participation over 5 years in Danish students aged 6-16-year-old.

Sports participation has potential to promote physical activity in youth. Unfortunately, sports participation and physical activity may decline from childhood to adolescence and into adulthood. Globally, only 20% of 13-15-year-olds meet the World Health Organisation recommendations for physical activity. This study aimed to investigate the 5-year trajectories of sports participation and their association with baseline motor performance in Danish school children as part of the Childhood Health Activity and Motor Performance School Study-Denmark (CHAMPS-DK), a school-based physical activity intervention study which investigated the health benefits of increased physical education lessons. Five distinct trajectories were identified, with group 1 maintained a stable trajectory of little to no sports participation, and group 2 showing a low decreasing trend. Group 3-5, the most sports active, demonstrated increasing sport participation at different rates. Baseline motor performance score was associated with the two most active sports participation groups. Students who were more physically active during school hours participated less in organised leisure time sports. This suggest focusing on improving motor performance in youth may support future sports participation and thus health-related physical activity. But also, that it might be necessary to engage and maintain children and adolescents in leisure time sports while implementing physical activity promotion interventions.

Reassessing the evidence of a survival advantage in Type 2 diabetes treated with metformin compared with controls without diabetes: a retrospective cohort study.

BACKGROUND: Previous research has suggested that individuals with Type 2 diabetes and initiated on metformin monotherapy present with a survival advantage compared with the general population without diabetes. This finding has generated considerable interest in the prophylactic use of metformin against age-related morbidity. METHODS: Utilizing Danish National Health Registers, we assessed differences in survival associated with metformin monotherapy for Type 2 diabetes compared with no diagnosis of diabetes in both singleton and discordant twin populations between 1996 and 2012. Data were analysed in both nested case-control and matched cohort study designs, with incidence rate ratios (IRRs) and hazard ratios estimated using conditional logistic regression and Cox proportional hazards regression, respectively. RESULTS: In case-control pairs matched on birth year and sex or co-twin (sex, birth year and familial factors), incident Type 2 diabetes with treatment by metformin monotherapy initiation compared with no diagnosis of diabetes was associated with increased mortality in both singletons (IRR = 1.52, 95% CI: 1.37, 1.68) and discordant twin pairs (IRR = 1.90, 95% CI: 1.35, 2.67). After adjusting for co-morbidities and social indicators, these associations were attenuated to 1.32 (95% CI: 1.16, 1.50) and 1.64 (95% CI: 1.10, 2.46), respectively. Increased mortality was observed across all levels of cumulative use and invariant to a range of study designs and sensitivity analyses. CONCLUSIONS: Treatment initiation by metformin monotherapy in Type 2 diabetes was not associated with survival equal or superior to that of the general population without diabetes. Our contrasting findings compared with previous research are unlikely to be the result of differences in epidemiological or methodological parameters.

The Effect of Wearable Tracking Devices on Cardiorespiratory Fitness Among Inactive Adults: Crossover Study.

BACKGROUND: Modern lifestyle is associated with a high prevalence of physical inactivity. OBJECTIVE: This study aims to investigate the effect of a wearable tracking device on cardiorespiratory fitness among inactive adults and to explore if personal characteristics and health outcomes can predict adoption of the device. METHODS: In total, 62 inactive adults were recruited for this study. A control period (4 weeks) was followed by an intervention period (8 weeks) where participants were instructed to register and follow their physical activity (PA) behavior on a wrist-worn tracking device. Data collected included estimated cardiorespiratory fitness, body composition, blood pressure, perceived stress levels, and self-reported adoption of using the tracking device. RESULTS: In total, 50 participants completed the study (mean age 48, SD 13 years, 84% women). Relative to the control period, participants increased cardiorespiratory fitness by 1.52 mL/kg/minute (95% CI 0.82-2.22; P<.001), self-reported PA by 140 minutes per week (95% CI 93.3-187.1; P<.001), daily step count by 982 (95% CI 492-1471; P<.001), and participants' fat percentage decreased by 0.48% (95% CI -0.84 to -0.13; P=.009). No difference was observed in blood pressure (systolic: 95% CI -2.16 to 3.57, P=.63; diastolic: 95% CI -0.70 to 2.55; P=.27) or perceived stress (95% CI -0.86 to 1.78; P=.49). No associations were found between adoption of the wearable tracking device and age, gender, personality, or education. However, participants with a low perceived stress at baseline were more likely to rate the use of a wearable tracking device highly motivating. CONCLUSIONS: Tracking health behavior using a wearable tracking device increases PA resulting in an improved cardiorespiratory fitness among inactive adults.

Impact of Cytomegalovirus Infection and Genetic Background on the Frequencies of Peripheral Blood Suppressor Cells in Human Twins.

Frequencies and proportions of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) in peripheral blood may be informative biomarkers for certain disease states. The influence of genetics and lifetime pathogen exposures on Treg and MDSC frequencies is largely unexplored. Cytomegalovirus (CMV) establishes a latent infection and causes an accumulation of late-differentiated CD8+ memory T cells, commonly associated with a lower frequency of naive cells. Here, analyzing peripheral blood mononuclear cells by multicolor flow cytometry, we found a tendency towards lower frequencies of CD4+CD25+FoxP3+ Tregs in CMV-seropositive than -seronegative middle-aged individuals (p = 0.054), whereas frequencies of lineage-negative CD14+HLA-DR-MDSCs were significantly lower in CMV-seropositive participants (p = 0.005). Assessing associations with the presence of antibodies against different CMV structural proteins, rather than merely assigning seropositivity or seronegativity, failed to yield any closer associations. Examining Treg subsets revealed at most a minor role of the individual's genetic background, based on an analysis of monozygotic (MZ, n = 42) versus dizygotic (DZ, n = 39) twin pairs from the Danish Twin Registry. The same was true for MDSCs. These initial results suggest that an immunological history of exposures is more important than genetics in determining overall human suppressor cell levels.

Genetic Influence on the Peripheral Differentiation Signature of Vδ2+ γδ and CD4+ αß T Cells in Adults.

Adaptive as well as innate immune traits are variously affected by environmental and genetic influences, but little is known about the impact of genetics on the diversity, differentiation and functionality of γδ T cells in humans. Here, we analyzed a cohort of 95 middle-aged twins from the Danish Twin Registry. The differentiation status of peripheral αß and γδ T cells was assessed by flow cytometry based on the surface expression of CD27, CD28 and CD45RA. Our data confirm the established associations of latent cytomegalovirus (CMV) infection with an accumulation of late differentiated memory T cells in the αß compartment as well as in the Vδ1+ γδ T cell subset. A comparison of differentiation phenotypes of γδ and αß T cells that were not affected by CMV seropositivity identified a significant correlation of early differentiated (ED) Vδ2+ and intermediate differentiated (ID) CD4+ T cells in monozygotic (MZ), but not in dizygotic (DZ) co-twins. Thus, our data suggest a genetic influence on the differentiation of γδ and αß T cell subsets.

The Use of Small Electronic Devices and Health: Feasibility of Interventions for a Forthcoming Crossover Design.

BACKGROUND: Modern lifestyle is heavily affected by technology such as smartphones, tablets, and other small computers; yet it remains unclear how our health and well-being are affected by the heavy use of these devices. OBJECTIVE: This feasibility study aims to test two different interventions of an experimental protocol for a forthcoming large-scale community-based study and get estimates of parameters for sample size calculation. The aim of the large-scale study is to investigate the effect of (1) a wearable tracking device on aerobic capacity (VO2max/kg) and the effect of (2) restricting media use on total sleep time. METHODS: Twenty healthy participants were included and equipped with a wrist-worn device tracking physical activity and sleep. Participants were allocated to either a physical activity group, which was instructed to use the wrist-worn device to support exercise, or a sleep silent group, which was instructed to remove or switch off all electronic devices in the bedroom (except the wrist-worn tracking device). The intervention lasted approximately 4 weeks. Data collected included blood pressure, submaximal cycle ergometer test, self-reported technology use, and compliance of using the wearable tracking device. RESULTS: All participants wore the wearable tracking device 95.8% (SD 4.4%) of the time. Participants in the physical activity group increased aerobic capacity from 30.38 (SD 8.98) to 32.1 (SD 8.71) mL/kg/min (t=-2.31, P=.046) and decreased their systolic blood pressure from 126.5 (SD 15.8) mm Hg to 121.8 (SD 11.7) mm Hg (t=2.72, P=.02). The sleep silent group prolonged their time offline before bedtime from 18.1 (SD 19.4) minutes to 27.2 (SD 17.3) minutes (t=-2.94, P=.02). CONCLUSIONS: The two interventions are feasible to conduct. Participants were willing to wear the tracking device on their wrist and restrict all media use in their bedroom and thereby reduce bedtime technology use. Our results also suggest that tracking physical activity using a wearable device is accompanied by noteworthy health benefits. We outline necessary adjustments for a forthcoming large-scale study.

Assessing the performance of a commercial multisensory sleep tracker.

Wearable sleep technology allows for a less intruding sleep assessment than PSG, especially in long-term sleep monitoring. Though such devices are less accurate than PSG, sleep trackers may still provide valuable information. This study aimed to validate a commercial sleep tracker, Garmin Vivosmart 4 (GV4), against polysomnography (PSG) and to evaluate intra-device reliability (GV4 vs. GV4). Eighteen able-bodied adults (13 females, M = 56.1 ± 12.0 years) with no self-reported sleep disorders were simultaneously sleep monitored by GV4 and PSG for one night while intra-device reliability was monitored in one participant for 23 consecutive nights. Intra-device agreement was considered sufficient (observed agreement = 0.85 ± 0.13, Cohen's kappa = 0.68 ± 0.24). GV4 detected sleep with high accuracy (0.90) and sensitivity (0.98) but low specificity (0.28). Cohen's kappa was calculated for sleep/wake detection (0.33) and sleep stage detection (0.20). GV4 significantly underestimated time awake (p = 0.001) including wake after sleep onset (WASO) (p = 0.001), and overestimated light sleep (p = 0.045) and total sleep time (TST) (p = 0.001) (paired t-test). Sleep onset and sleep end differed insignificantly from PSG values. Our results suggest that GV4 is not able to reliably describe sleep architecture but may allow for detection of changes in sleep onset, sleep end, and TST (ICC ≥ 0.825) in longitudinally followed groups. Still, generalizations are difficult due to our sample limitations.

Mechanisms underlying familial aggregation of exceptional health and survival: A three-generation cohort study.

The familial resemblance in length of adult life is very modest. Studies of parent-offspring and twins suggest that exceptional health and survival have a stronger genetic component than lifespan generally. To shed light on the underlying mechanisms, we collected information on Danish long-lived siblings (born 1886-1938) from 659 families, their 5379 offspring (born 1917-1982), and 10,398 grandchildren (born 1950-2010) and matched background population controls through the Danish 1916 Census, the Civil Registration System, the National Patient Register, and the Register of Causes of Death. Comparison with the background, population revealed consistently lower occurrence of almost all disease groups and causes of death in the offspring and the grandchildren. The expected incidence of hospitalization for mental and behavioral disorders was reduced by half in the offspring (hazard ratio 0.53, 95% confidence interval 0.45-0.62) and by one-third in the grandchildren (0.69, 0.61-0.78), while the numbers for tobacco-related cancer were 0.60 (0.51-0.70) and 0.71 (0.48-1.05), respectively. Within-family analyses showed a general, as opposed to specific, lowering of disease risk. Early parenthood and divorce were markedly less frequent in the longevity-enriched families, while economic and educational differences were small to moderate. The longevity-enriched families in this study have a general health advantage spanning three generations. The particularly low occurrence of mental and behavioral disorders and tobacco-related cancers together with indicators of family stability and only modest socioeconomic advantage implicate behavior as a key mechanism underlying familial aggregation of exceptional health and survival.

Dynamic Balance, but Not Precision Throw, Is Positively Associated with Academic Performance in Children.

We analyzed the longitudinal association between dynamic balance and throwing skill with academic performance and whether waist circumference mediated these relationships. The current one-year longitudinal study followed 1020 first (mean age 7.87 ± 0.34 years) through fifth grade (mean age 11.87 ± 0.37 years) children, measured twice in 2010 and 2011. Dynamic balance and precision throw were measures of motor competence. Waist circumference was measured with a measuring tape at the umbilicus level. Academic performance was assessed by a combined score of standardized Danish language and math tests. Structural equation modeling was used for analysis. All coefficients are standardized. Balance was associated with academic performance when both sexes were combined (ß = 0.126, 95% CI: 0.074 to 0.179), and waist circumference partially mediated the relationship (ß = 0.021, 95% CI: 0.008 to 0.034). For boys, balance was associated with academic performance, but waist circumference did not mediate the association. For girls, balance presented direct, mediated (via waist circumference), and total associations with academic performance. Dynamic balance is an important gross motor function that was longitudinally related to academic performance, and waist circumference partially mediated the relationship. Precision throw was not found to be associated with academic performance in both sexes combined or when analyzed separately.

Parallel Progress in Perceived Age and Life Expectancy.

BACKGROUND: Human life expectancy continues to rise in most populations. This rise not only leads to longer lives but also is accompanied by improved health at a given age, that is, recent cohorts show a reduction of biological age for a given chronological age. Despite or even because of the diversity of biomarkers of aging, an accurate quantification of a general shift in biological age across time has been challenging. METHODS: Here, we compared age perception of facial images taken in 2001 over a decade and related these changes in age perception to changes in life expectancy. RESULTS: We show that age perception changes substantially across time and parallels the progress in life expectancy. In 2012, people aged more than 70 years needed to look 2.3 years younger to be rated the same age as in 2002. CONCLUSIONS: Our results suggest that age perception reflects the past life events better than predicts future length of life, that is, it is written in your face how much you have aged so far. We draw this conclusion as age perception among elderly individuals paralleled changes in life expectancy at birth but not changes in remaining life expectancies. We suggest that changes in age perception should be explored for younger age classes to inform on aging processes, including whether aging is delayed or slowed with increasing life expectancy.

Clonal hematopoiesis in elderly twins: concordance, discordance, and mortality.

Clonal hematopoiesis (CH) of indeterminate potential (CHIP) is defined by mutations in myeloid cancer-associated genes with a variant allele frequency of at least 2%. Recent studies have suggested a possible genetic predisposition to CH. To further explore this phenomenon, we conducted a population-based study of 594 twins from 299 pairs aged 73 to 94 years, all with >20 years' follow-up. We sequenced DNA from peripheral blood with a customized 21-gene panel at a median coverage of 6179X. The casewise concordance rates for mutations were calculated to assess genetic predisposition. Mutations were identified in 214 (36%) of the twins. Whereas 20 twin pairs had mutations within the same genes, the exact same mutation was only observed in 2 twin pairs. No significant difference in casewise concordance between monozygotic and dizygotic twins was found for any specific gene, subgroup, or CHIP mutations overall, and no significant heritability could be detected. In pairs discordant for CHIP mutations, we tested if the affected twin died before the unaffected twin, as a direct measurement of the association of having CH when controlling for familial factors. A total of 127 twin pairs were discordant for carrying a mutation, and in 61 (48%) cases, the affected twin died first (P = .72). Overall, we did not find a genetic predisposition to CHIP mutations in this twin study. The previously described negative association of CHIP mutations on survival could not be confirmed in a direct comparison among twin pairs that were discordant for CHIP mutations.

The Danish Twin Registry: An Updated Overview.

The Danish Twin Registry (DTR) was established in the 1950s, when twins born from 1870 to 1910 were ascertained, and has since been extended to include twins from birth cohorts until 2009. The DTR currently comprises of more than 175,000 twins from the 140 birth cohorts. This makes the DTR the oldest nationwide twin register and among the largest in the world. The combination of data from several surveys, including biological samples and repeated measurements on the same individuals, and data from Danish national registers provides a unique resource for a wide range of twin studies. This article provides an updated overview of the data in the DTR: First, we provide a summary of the establishment of the register, the different ascertainment methods and the twins included; then follows an overview of major surveys conducted in the DTR since 1994 and a description of the DTR biobank, including a description of the molecular data created so far; finally, a short description is given of the linkage to Danish national registers at Statistics Denmark and some recent examples of studies using the various data resources in the DTR are highlighted.

Sex differences in the 1-year risk of dying following all-cause and cause-specific hospital admission after age 50 in comparison with a general and non-hospitalised population: a register-based cohort study of the Danish population.

OBJECTIVES: We examine the mortality of men and women within the first year after all-cause and cause-specific hospital admission to investigate whether the sex differences in mortality after hospitalisation are higher than in the corresponding general and non-hospitalised population. DESIGN: This is a population-based, longitudinal study with nationwide coverage. The study population was identified by linking the National Patient Register with the Central Population Register using a 5% random sample of the Danish population. SETTING: The population born between 1898 and 1961, who was alive and residing in Denmark after 1977, was followed up between 1977 and 2011 with respect to hospital admissions and mortality while aged 50-79. PRIMARY OUTCOME MEASURES: The absolute sex differences in the 1-year risk of dying after all-cause and cause-specific hospital admission. The hospitalised population sex differentials were then compared with the sex differences in a general and a non-hospitalised population, randomly matched by age, sex and hospitalisation status. RESULTS: The risk of dying was consistently higher for hospitalised men and women. At all ages, the absolute sex differences in mortality were largest in the hospitalised population, were smaller in the general population and were smallest in the non-hospitalised population. This pattern was consistent across all-cause admissions, and with respect to admissions for neoplasms, circulatory diseases and respiratory diseases. For all-cause hospital admissions, absolute sex differences in the 1-year risk of dying resulted in 43.8 excess male deaths per 1,000 individuals within the age range 50-79, while the levels were lower in the general and the non-hospitalised population, at levels of 13.5 and 6.6, respectively. CONCLUSIONS: This study indicates a larger male disadvantage in mortality following hospitalisation, pointing towards an association between the health status of a population and the magnitude of the female advantage in mortality.

Circulating, Cell-Free Micro-RNA Profiles Reflect Discordant Development of Dementia in Monozygotic Twins.

We aim to examine if circulating micro-RNA and cytokine levels associate with dementia diagnosis and cognitive scores. To test our hypothesis, we use plasma donated from 48 monozygotic twin pairs in 1997 and 46 micro-RNAs and 10 cytokines were quantified using microfluidic RT-qPCR and multiplex solid-phase immunoassays, respectively. Micro-RNA and cytokine profiling were examined for associations with dementia diagnoses in a longitudinal registry study or with cognitive scores at baseline. Thirty-six micro-RNAs and all cytokines were detected consistently. Micro-RNA profiles associate with diagnoses and cognitive scores at statistically significant levels while cytokine only showed trends pointing at chronic inflammation in twins having or developing dementia. The most notable findings were decreased miR-106a and miR-210, and increased miR-106b expression in twins with a dementia diagnosis. This pioneering evaluation of micro-RNA and cytokine and dementia diagnosis suggests micro-RNA targets in vasculogenesis, lipoprotein transport, and amyloid precursor protein genes.

Physical Fitness Is Longitudinally Associated With Academic Performance During Childhood and Adolescence, and Waist Circumference Mediated the Relationship.

PURPOSE: The current investigation aimed to investigate the longitudinal association between physical fitness and academic performance over 3 years in adolescents. A secondary aim was to determine to what extent waist circumference mediated the association between physical fitness and academic performance. METHODS: For the current study, 1020 students from first grade [mean age: 7.87 (0.34) y] to fifth grade [mean age: 11.87 (0.37) y] were monitored annually for 3 years (2010-2013). Physical fitness was assessed using the Andersen test, 5 × 5-m shuttle run, jump height, and grip strength tests and by constructing a composite score combining all 4 fitness tests. Academic performance was assessed by national standardized tests in Danish language and math. Generalized structural equation modeling was used to evaluate the relationships between these variables. RESULTS: The Andersen test (standardized ß = 0.15 SD), shuttle run (ß = -0.18 SD), jump height (ß = 0.10 SD), and the fitness composite score (ß = 0.23 SD) were positively associated with academic performance over 3 years. In addition, waist circumference partially mediated the association between physical fitness and academic performance. CONCLUSION: Thus, physical fitness abilities should be stimulated during childhood and early adolescence because of their positive association with academic performance.

Modulation of task-related cortical connectivity in the acute and subacute phase after stroke.

The functional relevance of cortical reorganization post-stroke is still not well understood. In this study, we investigated task-specific modulation of cortical connectivity between neural oscillations in key motor regions during the early phase after stroke. EEG and EMG recordings were examined from 15 patients and 18 controls during a precision grip task using the affected hand. Each patient attended two sessions in the acute and subacute phase (median of 3 and 34 days) post-stroke. Dynamic causal modelling (DCM) for induced responses was used to investigate task-specific modulations of oscillatory couplings in a bilateral network comprising supplementary motor area (SMA), dorsal premotor cortex (PMd) and primary motor cortex (M1). Fourteen models were constructed for each subject, and the input induced by the experimental manipulation (task) was set to inferior parietal lobule (IPL). Bayesian model selection favoured a fully connected model. A reduced coupling from SMA and intact M1 in the γ-band (31-48 Hz) to lesioned M1 in the ß-band (15-30 Hz) was observed in patients in the acute phase compared to controls. Behavioural performance improved significantly in the subacute phase, while an increased positive coupling from intact PMd to lesioned M1 and a less negative modulation from lesioned M1 to intact M1 were observed for patients compared to controls both from the γ-band to the ß-band. We infer that the observed differences in cross-frequency cortical interactions are important for functional recovery.

Musculoskeletal extremity pain in Danish school children - how often and for how long? The CHAMPS study-DK.

BACKGROUND: Musculoskeletal pain is common in childhood and adolescence, and may be long-lasting and recurrent. Musculoskeletal problems tend to follow adolescents into adulthood, and therefore it is important to design better prevention strategies and early effective treatment. To this end, we need in-depth knowledge about the epidemiology of musculoskeletal extremity problems in this age group, and therefore, the aim of this study was to determine the prevalence, frequency and course of musculoskeletal pain in the upper and lower extremities in a cohort of Danish school children aged 8-14 years at baseline. METHODS: This was a prospective 3-year school-based cohort study, with information about musculoskeletal pain collected in two ways. Parents answered weekly mobile phone text messages about the presence or absence of musculoskeletal pain in their children, and a clinical consultation was performed in a subset of the children. RESULTS: We found that approximately half the children had lower extremity pain every study year. This pain lasted on average for 8 weeks out of a study year, and the children had on average two and a half episodes per study year. Approximately one quarter of the children had upper extremity pain every study year that lasted on average 3 weeks during a study year, with one and a half episodes being the average. In general, there were more non-traumatic pain episodes compared with traumatic episodes in the lower extremities, whereas the opposite was true in the upper extremities. The most common anatomical pain sites were 'knee' and 'ankle/ft'. CONCLUSION: Lower extremity pain among children and adolescents is common, recurrent and most often of non-traumatic origin. Upper extremity pain is less common, with fewer and shorter episodes, and usually with a traumatic onset. Girls more frequently reported upper extremity pain, whereas there was no sex-related difference in the lower extremities. The most frequently reported locations were 'knee' and 'ankle/ft'.

Corticomuscular coherence in the acute and subacute phase after stroke.

OBJECTIVE: Stroke is one of the leading causes of physical disability due to damage of the motor cortex or the corticospinal tract. In the present study we set out to investigate the role of adaptations in the corticospinal pathway for motor recovery during the subacute phase after stroke. METHODS: We examined 19 patients with clinically diagnosed stroke and 18 controls. The patients had unilateral mild to moderate weakness of the hand. Each patient attended two sessions at approximately 3days (acute) and 38days post stroke (subacute). Task-related changes in the communication between motor cortex and muscles were evaluated from coupling in the frequency domain between EEG and EMG during movement of the paretic hand. RESULTS: Corticomuscular coherence (CMC) and intermuscular coherence (IMC) were reduced in patients as compared to controls. Paretic hand motor performance improved within 4-6weeks after stroke, but no change was observed in CMC or IMC. CONCLUSIONS: CMC and IMC were reduced in patients in the early phase after stroke. However, changes in coherence do not appear to be an efficient marker for early recovery of hand function following stroke. SIGNIFICANCE: This is the first study to demonstrate sustained reduced coherence in acute and subacute stroke.