Development and evaluation of the Capability, Opportunity, and Motivation to deliver Physical Activity in School Scale (COM-PASS).

BACKGROUND: Teachers are recognized as 'key agents' for the delivery of physical activity programs and policies in schools. The aim of our study was to develop and evaluate a tool to assess teachers' capability, opportunity, and motivation to deliver school-based physical activity interventions. METHODS: The development and evaluation of the Capability, Opportunity, and Motivation to deliver Physical Activity in School Scale (COM-PASS) involved three phases. In Phase 1, we invited academic experts to participate in a Delphi study to rate, provide recommendations, and achieve consensus on questionnaire items that were based on the Capability, Opportunity, and Motivation Behavior (COM-B) model. Each item was ranked on the degree to which it matched the content of the COM-B model, using a 5-point scale ranging from '1 = Poor match' to '5 = Excellent match'. In Phase 2, we interviewed primary and secondary school teachers using a 'think-aloud' approach to assess their understanding of the items. In Phase 3, teachers (n = 196) completed the COM-PASS to assess structural validity using confirmatory factor analysis (CFA). RESULTS: Thirty-eight academic experts from 14 countries completed three rounds of the Delphi study. In the first round, items had an average rating score of 4.04, in the second round 4.51, and in the third (final) round 4.78. The final tool included 14 items, which related to the six constructs of the COM-B model: physical capability, psychological capability, physical opportunity, social opportunity, reflective motivation, and automatic motivation. In Phase 2, ten teachers shared their interpretation of COM-PASS via a 20-min interview, which resulted in minor changes. In Phase 3, CFA of the 3-factor model (i.e., capability, opportunity, and motivation) revealed an adequate fit to the data (χ2 = 122.6, p < .001, CFI = .945, TLI = .924, RMSEA = .066). The internal consistencies of the three subscale scores were acceptable (i.e., capability: α = .75, opportunity: α = .75, motivation: α = .81). CONCLUSION: COM-PASS is a valid and reliable tool for assessing teachers' capability, opportunity, and motivation to deliver physical activity interventions in schools. Further studies examining additional psychometric properties of the COM-PASS are warranted.

Using multi-event hydrologic and hydraulic signatures from water level sensors to diagnose locations of uncertainty in integrated urban drainage models used in living digital twins.

Digital twins of urban drainage systems require simulation models that can adequately replicate the physical system. All models have their limitations, and it is important to investigate when and where simulation results are acceptable and to communicate the level of performance transparently to end users. This paper first defines a classification of four possible 'locations of uncertainty' in integrated urban drainage models. It then develops a structured framework for identifying and diagnosing various types of errors. This framework compares model outputs with in-sewer water level observations based on hydrologic and hydraulic signatures. The approach is applied on a real case study in Odense, Denmark, with examples from three different system sites: a typical manhole, a small flushing chamber, and an internal overflow structure. This allows diagnosing different model errors ranging from issues in the underlying asset database and missing hydrologic processes to limitations in the model software implementation. Structured use of signatures is promising for continuous, iterative improvements of integrated urban drainage models. It also provides a transparent way to communicate the level of model adequacy to end users.

Heterogeneous Clusters of Phthalocyanine and Water Prepared and Probed in Superfluid Helium Nanodroplets.

Superfluid helium nanodroplets comprised of thousands to millions of helium atoms can serve as a reactor for the synthesis of heterogeneous molecular clusters at cryogenic conditions. The cluster synthesis occurs via consecutive pick-up of the cluster building blocks by the helium droplet and their subsequent coalescence within the droplet. The effective collision cross section of the building blocks is determined by the helium droplet size and thus exceeds by orders of magnitude that of a reactive collision in the gas phase. Moreover, the cryogenic helium environment (at 0.38 K) as a host promotes the formation of metastable cluster configurations. The question arises as to the extent of the actual involvement of the helium environment in the cluster formation. The present study deals with clusters of single phthalocyanine (Pc) molecules with single water molecules. A large fluorophore such as Pc offers several sites where the water molecule can attach. The resulting isomeric variants of the Pc-H2O complex can be selectively identified by electronic spectroscopy. We compare the experimental electronic spectra of the Pc-H2O complex generated in superfluid helium nanodroplets with the results of quantum-chemical calculations on the same cluster but under gas-phase conditions. The number of isomeric variants observed in the helium droplet experiment comes out the same as that obtained from our gas-phase calculations.

Variable impact of tizanidine on the medium latency reflex of upper and lower limbs.

Sudden limb displacement evokes a complex sequence of compensatory muscle activity. Following the short-latency reflex and preceding voluntary reactions is an epoch termed the medium-latency reflex (MLR) that could reflect spinal processing of group II muscle afferents. One way to test this possibility is oral ingestion of tizanidine, an alpha-2 adrenergic agonist that inhibits the interneurons transmitting group II signals onto spinal motor neurons. We examined whether group II afferents contribute to MLR activity throughout the major muscles that span the elbow and shoulder. MLRs of ankle muscles were also tested during walking on the same day, in the same participants as well as during sitting in a different group of subjects. In contrast to previous reports, the ingestion of tizanidine had minimal impact on MLRs of arm or leg muscles during motor actions. A significant decrease in magnitude was observed for 2/16 contrasts in arm muscles and 0/4 contrasts in leg muscles. This discrepancy with previous studies could indicate that tizanidine's efficacy is altered by subtle changes in protocol or that group II afferents do not substantially contribute to MLRs.

Estimation of the transmission dynamics of African swine fever virus within a swine house.

The spread of African swine fever virus (ASFV) threatens to reach further parts of Europe. In countries with a large swine production, an outbreak of ASF may result in devastating economic consequences for the swine industry. Simulation models can assist decision makers setting up contingency plans. This creates a need for estimation of parameters. This study presents a new analysis of a previously published study. A full likelihood framework is presented including the impact of model assumptions on the estimated transmission parameters. As animals were only tested every other day, an interpretation was introduced to cover the weighted infectiousness on unobserved days for the individual animals (WIU). Based on our model and the set of assumptions, the within- and between-pen transmission parameters were estimated to ß w = 1·05 (95% CI 0·62-1·72), ß b = 0·46 (95% CI 0·17-1·00), respectively, and the WIU = 1·00 (95% CI 0-1). Furthermore, we simulated the spread of ASFV within a pig house using a modified SEIR-model to establish the time from infection of one animal until ASFV is detected in the herd. Based on a chosen detection limit of 2·55% equivalent to 10 dead pigs out of 360, the disease would be detected 13-19 days after introduction.

Acute exercise and motor memory consolidation: Does exercise type play a role?

A single bout of high-intensity exercise can augment off-line gains in skills acquired during motor practice. It is currently unknown if the type of physical exercise influences the effect on motor skill consolidation. This study investigated the effect of three types of high-intensity exercise following visuomotor skill acquisition on the retention of motor memory in 40 young (25.3 ±3.6 years), able-bodied male participants randomly assigned to one of four groups either performing strength training (STR), circuit training (CT), indoor hockey (HOC) or rest (CON). Retention tests of the motor skill were performed 1 (R1h) and 24 h (R1d) post acquisition. For all exercise groups, mean motor performance scores decreased at R1h compared to post acquisition (POST) level; STR (P = 0.018), CT (P = 0.02), HOC (P = 0.014) and performance scores decreased for CT compared to CON (P = 0.049). Mean performance scores increased from POST to R1d for all exercise groups; STR (P = 0.010), CT (P = 0.020), HOC (P = 0.007) while performance scores for CON decreased (P = 0.043). Changes in motor performance were thus greater for STR (P = 0.006), CT (P < 0.001) and HOC (P < 0.001) compared to CON from POST to R1d. The results demonstrate that high-intensity, acute exercise can lead to a decrease in motor performance assessed shortly after motor skill practice (R1h), but enhances offline effects promoting long-term retention (R1d). Given that different exercise modalities produced similar positive off-line effects on motor memory, we conclude that exercise-induced effects beneficial to consolidation appear to depend primarily on the physiological stimulus rather than type of exercise and movements employed.

Effect of a school environment intervention on adolescent adiposity and physical fitness.

The aim of this study was to evaluate the effect of an intervention targeting the physical and organizational school environment for noncurricular physical activity (SPACE) on adiposity, aerobic fitness, and musculo-skeletal strength in Danish adolescents. The study used a cluster randomized controlled design. Fourteen schools and 1348 adolescents aged 11-14 years were included at baseline. Seven schools were randomized to the intervention, which was designed to change the organizational and physical environment of the school. The analysis revealed no significant differences between the adolescents in the intervention group compared to the comparison group after a 2-year follow-up. Adjusted for baseline, sex, age, and clustering within schools, the difference between the intervention schools compared to the comparison schools was 6 m in the shuttle run test [95% confidence interval (CI): -21; 33], 0.2 cm in waist circumference (95% CI: -2.6; 3.1), and -1.1 kg in handgrip strength (95% CI: -2.2; -0.1). The results did not provide evidence for the effect of the intervention on adiposity, aerobic fitness, or musculo-skeletal strength in adolescents. Reasons for not finding an effect could be related to both the design and the implementation of the intervention.

Adult glucose metabolism in extremely birthweight-discordant monozygotic twins.

AIMS/HYPOTHESIS: Low birthweight (BW) is associated with increased risk of type 2 diabetes. We compared glucose metabolism in adult BW-discordant monozygotic (MZ) twins, thereby controlling for genetic factors and rearing environment. METHODS: Among 77,885 twins in the Danish Twin Registry, 155 of the most BW-discordant MZ twin pairs (median BW difference 0.5 kg) were assessed using a 2 h oral glucose tolerance test with sampling of plasma (p-)glucose, insulin, C-peptide, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1. HOMA for beta cell function (HOMA-ß) and insulin resistance (HOMA-IR), and also insulin sensitivity index (BIGTT-SI) and acute insulin response (BIGTT-AIR), were calculated. Subgroup analyses were performed in those with: (1) double verification of BW difference; (2) difference in BW >0.5 kg; and (3) no overt metabolic disease (type 2 diabetes, hyperlipidaemia or thyroid disease). RESULTS: No intra-pair differences in p-glucose, insulin, C-peptide, incretin hormones, HOMA-ß, HOMA-IR or BIGTT-SI were identified. p-Glucose at 120 min was higher in the twins with the highest BW without metabolic disease, and BIGTT-AIR was higher in those with the highest BW although not in pairs with a BW difference of >0.5 kg. CONCLUSIONS/INTERPRETATION: BW-discordant MZ twins provide no evidence for a detrimental effect of low BW on glucose metabolism in adulthood once genetic factors and rearing environment are controlled for.

Introduced European bison (Bison bonasus) in a confined forest district: A ten year parasitological survey.

In the year 2012 a total of seven individuals (one bull and six cows) of European bison (Bison bonasus) were introduced to a fenced 200 ha area in a forest district (Almindingen, Island Bornholm, Denmark) in the Baltic Sea. In 2017 the herd was supplemented by introduction of another bull. The animals all originated from a population in the Polish Bialowieza forest. Faecal samples were recovered with intervals and subjected to a copro-parasitological investigation (applying egg flotation, sedimentation and Baermann technique). In addition, parasites were sampled during necropsy of animals euthanized or found dead three years after introduction. The animals carried a range of parasite types including trematodes (liver fluke Fasciola and rumen fluke), cestodes (Moniezia), nematodes (Dictyocaulus viviparus, trichurids, and other gastrointestinal nematodes (GIN) including Trichostrongylus axei and Haemonchus contortus). Egg and larval morphology also suggested presence of GIN genera Nematodirus, Ostertagia and Cooperia. The trematodes did not establish a life cycle in the recipient area, as judged by examination of calves born in the new area, but the cestode and several nematode species occurred in these animals. Especially Dictyocaulus viviparus was successfully spread and occurred together with GIN at moderate to high infection intensities at most sampling points. The reproduction among bison in the herd was high during the first few years. The exact birth rate is unknown but up to 24 calves are believed to be born during the ten year study period. Mortality among adults and calves occurred and in early June 2022 the total number of live animals was 11 (seven males, three females, one calf). The possible impact of the parasite infections on the bison health and future wildlife infection status is discussed.

Modelling conjugation with stochastic differential equations.

Conjugation is an important mechanism involved in the transfer of resistance between bacteria. In this article a stochastic differential equation based model consisting of a continuous time state equation and a discrete time measurement equation is introduced to model growth and conjugation of two Enterococcus faecium strains in a rich exhaustible media. The model contains a new expression for a substrate dependent conjugation rate. A maximum likelihood based method is used to estimate the model parameters. Different models including different noise structure for the system and observations are compared using a likelihood-ratio test and Akaike's information criterion. Experiments indicating conjugation on the agar plates selecting for transconjugants motivates the introduction of an extended model, for which conjugation on the agar plate is described in the measurement equation. This model is compared to the model without plate conjugation. The modelling approach described in this article can be applied generally when modelling dynamical systems.

Activity profile and physiological response to football training for untrained males and females, elderly and youngsters: influence of the number of players.

The present study examined the activity profile, heart rate and metabolic response of small-sided football games for untrained males (UM, n=26) and females (UF, n=21) and investigated the influence of the number of players (UM: 1v1, 3v3, 7v7; UF: 2v2, 4v4 and 7v7). Moreover, heart rate response to small-sided games was studied for children aged 9 and 12 years (C9+C12, n=75), as well as homeless (HM, n=15), middle-aged (MM, n=9) and elderly (EM, n=11) men. During 7v7, muscle glycogen decreased more for UM than UF (28 +/- 6 vs 11 +/- 5%; P<0.05) and lactate increased more (18.4 +/- 3.6 vs 10.8 +/- 2.1 mmol kg(-1) d.w.; P<0.05). For UM, glycogen decreased in all fiber types and blood lactate, glucose and plasma FFA was elevated (P<0.05). The mean heart rate (HR(mean)) and time >90% of HR(max) ranged from 147 +/- 4 (EM) to 162 +/- 2 (UM) b.p.m. and 10.8 +/- 1.5 (UF) to 47.8 +/- 5.8% (EM). Time >90% of HR(max) (UM: 16-17%; UF: 8-13%) and time spent with high speed running (4.1-5.1%) was similar for training with 2-14 players, but more high-intensity runs were performed with few players (UM 1v1: 140 +/- 17; UM 7v7: 97 +/- 5; P<0.05): Small-sided games were shown to elucidate high heart rates for all player groups, independently of age, sex, social background and number of players, and a high number of intense actions both for men and women. Thus, small-sided football games appear to have the potential to create physiological adaptations and improve performance with regular training for a variety of study groups.

Long-term musculoskeletal and cardiac health effects of recreational football and running for premenopausal women.

We examined long-term musculoskeletal and cardiac adaptations elicited by recreational football (FG, n=9) and running (RG, n=10) in untrained premenopausal women in comparison with a control group (CG, n=9). Training was performed for 16 months ( approximately 2 weekly 1-h sessions). For FG, right and left ventricular end-diastolic diameters were increased by 24% and 5% (P<0.05), respectively, after 16 months. Right ventricular systolic function measured by tricuspid annular plane systolic excursion (TAPSE) increased (P<0.05) in FG after 4 months and further (P<0.05) after 16 months (15% and 32%, respectively). In RG and CG, cardiac structure, E/A and TAPSE remained unchanged. For FG, whole-body bone mineral density (BMD) was 2.3% and 1.3% higher (P<0.05) after 16 months, than after 4 and 0 months, respectively, with no changes for RG and CG. FG demonstrated substantial improvements (P<0.05) in fast (27% and 16%) and slow (16% and 17%) eccentric muscle strength and rapid force capacity (Imp30ms: 66% and 65%) after 16 months compared with 4 and 0 months, with RG improving Imp30ms by 64% and 46%. In conclusion, long-term recreational football improved muscle function, postural balance and BMD in adult women with a potential favorable influence on the risk of falls and fractures. Moreover, football training induced consistent cardiac adaptations, which may have implications for long-term cardiovascular health.

Antibiotic resistance in Pseudomonas aeruginosa strains with increased mutation frequency due to inactivation of the DNA oxidative repair system.

The chronic Pseudomonas aeruginosa infection of the lungs of cystic fibrosis (CF) patients is characterized by the biofilm mode of growth and chronic inflammation dominated by polymorphonuclear leukocytes (PMNs). A high percentage of P. aeruginosa strains show high frequencies of mutations (hypermutators [HP]). P. aeruginosa is exposed to oxygen radicals, both those generated by its own metabolism and especially those released by a large number of PMNs in response to the chronic CF lung infection. Our work therefore focused on the role of the DNA oxidative repair system in the development of HP and antibiotic resistance. We have constructed and characterized mutT, mutY, and mutM mutants in P. aeruginosa strain PAO1. The mutT and mutY mutants showed 28- and 7.5-fold increases in mutation frequencies, respectively, over that for PAO1. These mutators had more oxidative DNA damage (higher levels of 7,8-dihydro-8-oxodeoxyguanosine) than PAO1 after exposure to PMNs, and they developed resistance to antibiotics more frequently. The mechanisms of resistance were increased beta-lactamase production and overexpression of the MexCD-OprJ efflux-pump. Mutations in either the mutT or the mutY gene were found in resistant HP clinical isolates from patients with CF, and complementation with wild-type genes reverted the phenotype. In conclusion, oxidative stress might be involved in the development of resistance to antibiotics. We therefore suggest the possible use of antioxidants for CF patients to prevent the development of antibiotic resistance.

Candidate region linkage analysis in twins discordant or concordant for depression symptomatology.

Genetic risk factors contribute considerably to both clinical affective disorders and subsyndromal mood level. There is moreover evidence to suggest that the genetic basis of bipolar disorder and unipolar depression overlap to some extent, and several linkage analyses have suggested evidence for a common susceptibility locus in affective disorders on chromosome 12q24. In this study we investigated the chromosome 12 candidate region for linkage to the mean level of depression symptomatology, over a 10-year follow-up, using a highly informative sample of concordant and discordant twin pairs selected from 4,731 participants of the Longitudinal Study of Ageing Danish Twins. Our results showed suggestive evidence of linkage to this region with a peak LOD score of 1.91 for marker D12S1634 located at 148 cM, and thus indicates that the previously identified disease locus at 12q24 is also a general vulnerability locus affecting the normal range of mood.

Epigenome-wide association study of depression symptomatology in elderly monozygotic twins.

Depression is a severe and debilitating mental disorder diagnosed by evaluation of affective, cognitive and physical depression symptoms. Severity of these symptoms strongly impacts individual's quality of life and is influenced by a combination of genetic and environmental factors. One of the molecular mechanisms allowing for an interplay between these factors is DNA methylation, an epigenetic modification playing a pivotal role in regulation of brain functioning across lifespan. The aim of this study was to investigate if there are DNA methylation signatures associated with depression symptomatology in order to identify molecular mechanisms contributing to pathophysiology of depression. We performed an epigenome-wide association study (EWAS) of continuous depression symptomatology score measured in a cohort of 724 monozygotic Danish twins (346 males, 378 females). Through EWAS analyses adjusted for sex, age, flow-cytometry based blood cell composition, and twin relatedness structure in the data we identified depression symptomatology score to be associated with blood DNA methylation levels in promoter regions of neuropsin (KLK8, p-value = 4.7 × 10-7) and DAZ associated protein 2 (DAZAP2, p-value = 3.13 × 10-8) genes. Other top associated probes were located in gene bodies of MAD1L1 (p-value = 5.16 × 10-6), SLC29A2 (p-value = 6.15 × 10-6) and AKT1 (p-value = 4.47 × 10-6), all genes associated before with development of depression. Additionally, the following three measures (a) DNAmAge (calculated with Horvath and Hannum epigenetic clock estimators) adjusted for chronological age, (b) difference between DNAmAge and chronological age, and (c) DNAmAge acceleration were not associated with depression symptomatology score in our cohort. In conclusion, our data suggests that depression symptomatology score is associated with DNA methylation levels of genes implicated in response to stress, depressive-like behaviors, and recurrent depression in patients, but not with global DNA methylation changes across the genome.

Urine 5-hydroxyindoleacetic acid in Cavalier King Charles spaniels with preclinical myxomatous mitral valve disease.

Higher concentrations of circulating serotonin have been reported in Cavalier King Charles spaniels (CKCS) compared to other dog breeds. The CKCS is also a breed highly predisposed to myxomatous mitral valve disease (MMVD). The aim of this study was to determine urine concentrations of 5-hydroxyindoleacetic acid (5-HIAA), the major metabolite and excretion product of serotonin, in a population of CKCS with preclinical MMVD, and to evaluate whether urine 5-HIAA concentrations were associated with MMVD severity, dog characteristics, setting for urine sampling, platelet count, and serotonin concentration in serum and platelet-poor plasma (PPP). The study population consisted of 40 privately-owned CKCS (23 females; 17 males) with and without preclinical MMVD as follows: American College of Veterinary Internal Medicine (ACVIM) group A (n = 11), ACVIM group B1 (n = 21) and ACVIM group B2 (n = 8). Urine 5-HIAA concentrations were not significantly associated with preclinical MMVD disease, platelet count or circulating concentrations of serotonin (in serum and PPP; P > 0.05). Females had higher 5-HIAA concentrations than males in morning urine collected at home (females, 3.1 [2.9-3.7] µmol/mmol creatinine [median and quartiles]; males, 1.7 [1.2-2.2] µmol/mmol creatinine; P = 0.0002) and urine collected at the clinic (females, 3.5 [3.1-3.9] µmol/mmol creatinine; males, 1.6 [1.3-2.1] µmol/mmol creatinine; P < 0.0001). Five-HIAA concentrations in urine collected at home and at the clinic were significantly associated (P = 0.0004; r = 0.73), and higher concentrations were found in urine collected at the clinic (P = 0.013). Urine 5-HIAA concentration was influenced by sex and setting of urine sampling. Urine 5-HIAA concentration was not associated with MMVD severity or circulating concentrations of serotonin in CKCS with preclinical disease.

Maximum Likelihood based comparison of the specific growth rates for P. aeruginosa and four mutator strains.

The specific growth rate for P. aeruginosa and four mutator strains mutT, mutY, mutM and mutY-mutM is estimated by a suggested Maximum Likelihood, ML, method which takes the autocorrelation of the observation into account. For each bacteria strain, six wells of optical density, OD, measurements are used for parameter estimation. The data is log-transformed such that a linear model can be applied. The transformation changes the variance structure, and hence an OD-dependent variance is implemented in the model. The autocorrelation in the data is demonstrated, and a correlation model with an exponentially decaying function of the time between observations is suggested. A model with a full covariance structure containing OD-dependent variance and an autocorrelation structure is compared to a model with variance only and with no variance or correlation implemented. It is shown that the model that best describes data is a model taking into account the full covariance structure. An inference study is made in order to determine whether the growth rate of the five bacteria strains is the same. After applying a likelihood-ratio test to models with a full covariance structure, it is concluded that the specific growth rate is the same for all bacteria strains. This study highlights the importance of carrying out an explorative examination of residuals in order to make a correct parametrization of a model including the covariance structure. The ML method is shown to be a strong tool as it enables estimation of covariance parameters along with the other model parameters and it makes way for strong statistical tools for inference studies.

Symmetric Dimethylarginine in Cats with Hypertrophic Cardiomyopathy and Diabetes Mellitus.

BACKGROUND: Symmetric dimethylarginine (SDMA) has been increasingly used as a marker of early chronic kidney disease (CKD) in cats, but little is known about the influence of comorbidities on SDMA in this species. HYPOTHESIS: Hypertrophic cardiomyopathy (HCM) and diabetes mellitus (DM), independently of CKD, are associated with changes in serum SDMA. ANIMALS: Ninety-four cats (17 with CKD, 40 with HCM, 17 with DM, and 20 healthy controls). METHODS: Case-control study. Clinical examination, echocardiography, ECG, blood pressure, CBC, biochemistry, thyroxine, and SDMA measurement were performed. Urinalysis was performed in controls and cats with CKD and DM. Analysis of variance was used to compare overall differences in the log-transformed SDMA data among groups. A random forest algorithm was applied to explore which clinical and other factors influenced serum SDMA. RESULTS: Median (range) serum SDMA for the renal group (positive control) was 19 (10-93) µg/dL, whereas for the control group (negative control), it was 10 (5-15) µg/dL. For the cardiac and diabetic groups, serum SDMA was 9 (4-24) µg/dL and 7 (3-11) µg/dL, respectively. The renal group had significantly higher SDMA concentrations and the diabetic group significantly lower SDMA concentrations compared to all other groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum SDMA concentrations in cats with HCM were not significantly different from those of healthy control cats. Cats with DM, however, had significantly lower SDMA concentrations than controls, a finding that needs further investigation and should be kept in mind when evaluating renal function of cats with this endocrinopathy.

Progressive practice promotes motor learning and repeated transient increases in corticospinal excitability across multiple days.

BACKGROUND: A session of motor skill learning is accompanied by transient increases in corticospinal excitability(CSE), which are thought to reflect acute changes in neuronal connectivity associated with improvements in sensorimotor performance. Factors influencing changes in excitability and motor skill with continued practice remain however to be elucidated. OBJECTIVE/HYPOTHESIS: Here we investigate the hypothesis that progressive motor practice during consecutive days can induce repeated transient increases in corticospinal excitability and promote motor skill learning. METHODS: Changes in motor performance and CSE were assessed during 4 consecutive days of skill learning and 8 days after the last practice session. CSE was assessed as area under recruitment curves(RC) using transcranial magnetic stimulation(TMS). Two groups of participants(n = 12) practiced a visuomotor tracking-task with task difficulty progressively increased with individual proficiency(PPG) or with the same task level throughout all 4 days(NPPG). RESULTS: Progressive practice resulted in superior motor learning compared to NPPG(p < 0.001). Whereas NPPG displayed increased CSE following only the first day of practice(p < 0.001), progressive motor practice was accompanied by increases in CSE on both the first and the final session of motor practice(p = 0.006). Eight days after ended practice, the groups showed similar CSE, but PPG maintained superior performance at a skilled task level and transfer task performance(p < 0.005,p = 0.029). CONCLUSION: The results demonstrate that progressive practice promotes both motor learning and repeated increases in CSE across multiple days. While changes in CSE did not relate to learning our results suggest that they signify successful training. Progressive practice is thus important for optimizing neurorehabilitation and motor practice protocols in general.

Blood DNA methylation age is not associated with cognitive functioning in middle-aged monozygotic twins.

The epigenetic clock, also known as DNA methylation age (DNAmAge), represents age-related changes of DNA methylation at multiple sites of the genome and is suggested to be a biomarker for biological age. Elevated blood DNAmAge is associated with all-cause mortality, with the strongest effects reported in a recent intrapair twin study where epigenetically older twins had increased mortality risk in comparison to their co-twins. In the study presented here, we hypothesize that DNAmAge in blood is associated with cross-sectional and longitudinal cognitive abilities in middle-aged individuals. In 486 monozygotic twins, we investigated the association of DNAmAge, difference between DNAmAge and chronological age and age acceleration with cognition. Despite using a powerful paired twin design, we found no evidence for association of blood DNAmAge with cognitive abilities. This observation was confirmed in unpaired analyses, where DNAmAge initially correlated with cognitive abilities, until adjusting for chronological age. Overall, our study shows that for middle-aged individuals DNAmAge calculated in blood does not correlate with cognitive abilities.