Low Physical Activity Level and Short Sleep Duration Are Associated with an Increased Cardio-Metabolic Risk Profile: A Longitudinal Study in 8-11 Year Old Danish Children

Background

As cardio-metabolic risk tracks from childhood to adulthood, a better understanding of the relationship between movement behaviors (physical activity, sedentary behavior and sleep) and cardio-metabolic risk in childhood may aid in preventing metabolic syndrome (MetS) in adulthood.

Objective

To examine independent and combined cross-sectional and longitudinal associations between movement behaviors and the MetS score in 8-11 year old Danish children.

Design

Physical activity, sedentary time and sleep duration (seven days and eight nights) were assessed by accelerometer and fat mass index (fat mass/height²) was assessed using Dual-energy X-ray absorptiometry. The MetS-score was based on z-scores of waist circumference, mean arterial blood pressure, homeostatic model assessment of insulin resistance, triglycerides and high density lipoprotein cholesterol. All measurements were taken at three time points separated by 100 days. Average of the three measurements was used as habitual behavior in the cross-sectional analysis and changes from first to third measurement was used in the longitudinal analysis.

Results

723 children were included. In the cross-sectional analysis, physical activity was negatively associated with the MetS-score (P<0.03). In the longitudinal analysis, low physical activity and high sedentary time were associated with an increased MetS-score (all P<0.005); however, after mutual adjustments for movement behaviors, physical activity and sleep duration, but not sedentary time, were associated with the MetS-score (all P<0.03). Further adjusting for fat mass index while removing waist circumference from the MetS-score rendered the associations no longer statistically significant (all P>0.17). Children in the most favorable tertiles of changes in moderate-to-vigorous physical activity, sleep duration and sedentary time during the 200-day follow-up period had an improved MetS-score relative to children in the opposite tertiles (P = 0.005).

Conclusion

The present findings indicate that physical activity, sedentary time and sleep duration should all be targeted to improve cardio-metabolic risk markers in childhood; this is possibly mediated by adiposity.     

Seasonal Dynamics of CO2 Flux Across the Surface of Shallow Temperate Lakes

We used data collected from 1989 to 2009 from 151 shallow (mean depth < 3 m) temperate lakes in Denmark to explore the influence of lake trophic status, surface area and catchment size on the seasonal dynamics of the air–water flux of CO₂. Monthly CO₂ fluxes were derived from measurements of acid neutralizing capacity (ANC), pH, ionic strength, temperature, and wind speed. CO₂ fluxes exhibited large seasonal variability, in particular in oligo-mesotrophic lakes. Most of the lakes emitted CO₂ during winter (median rates ranging 300–1,900 mg C m⁻² day⁻¹), and less CO₂ during summer or, in the case of some of the highly eutrophic lakes, retained CO₂ during summer. We found that seasonal CO₂ fluxes were strongly negatively correlated with pH (r = −0.65, P < 0.01), which in turn was correlated with chlorophyll a concentrations (r = 0.48, P < 0.01). Our analysis suggests that lake trophic status (a proxy for pelagic production) interacts with the lake ANC to drive the seasonal dynamics of CO₂ fluxes, largely by changing pH and thereby the equilibrium of the free CO₂ and bicarbonate relation. Long-term observations from four lakes, which have all undergone a period of oligotrophication during the past two decades, provide further evidence that CO₂ efflux generally increases as trophic status decreases, as a consequence of decreased pH. Across these four lakes, the annual average CO₂ emission has increased by 32% during the past two decades, thus, demonstrating the strong link between lake trophic status and CO₂ flux.     

Treatment with the vascular disrupting agent combretastatin is associated with impaired AQP2 trafficking and increased urine output

Combretastatin A-4 disodium phosphate (CA4P) is a vascular disrupting agent known to mediate its effects primarily on tumor blood vessels. CA4P has previously been shown to induce a significant increase in mean arterial blood pressure and in hemoglobin concentration in mice. In the present study, we examined whether this is associated with a general leakage of water into certain tissues or with changes in renal water handling. Munich-Wistar rats received either CA4P (30 mg/kg body wt) or saline intraperitoneally as a bolus injection. One hour later, hemoglobin concentration and mean blood pressure increased significantly. MRI showed no significant changes in tissue water content following CA4P administration. However, urine output and salt excretion increased 1 h after CA4P treatment, without changes in urinary and medullary osmolality. Aquaporin 2 (AQP2) mRNA levels in kidney inner medulla did not change 1 h after CA4P treatment, but semiquantitative confocal laser-scanning microscopy analysis demonstrated a decrease in phosphorylated AQP2 (pS256-AQP2) apical distribution within the collecting ducts of CA4P-treated rats compared with the characteristic apical localization in control rats. Furthermore, we demonstrated that CA4P cause disruption of microtubules and a weaker apical labeling of pS256-AQP2 in collecting duct principal cells within 1 h. In conclusion, our data indicate that water escapes from the vascular system after CA4P treatment, and it may take place primarily through a renal mechanism. The CA4P-mediated increase in urine output seems to be a local effect in the collecting ducts due to reduced AQP2 trafficking to the apical plasma membrane.     

Disruption of cyclooxygenase-2 prevents downregulation of cortical AQP2 and AQP3 in response to bilateral ureteral obstruction in the mouse

Bilateral ureteral obstruction (BUO) in rats is associated with increased cyclooxygenase type 2 (COX-2) expression, and selective COX-2 inhibition prevents downregulation of aquaporins (AQPs) in response to BUO. It was hypothesized that a murine model would display similar changes in renal COX-2 and AQPs upon BUO and that targeted disruption of COX-2 protects against BUO-induced suppression of collecting duct AQPs. COX-2(-/-) and wild-type littermates (C57BL/6) were employed to determine COX-1, -2, AQP2, and AQP3 protein abundances and localization after BUO. In a separate series, sham and BUO wild-type mice were treated with a selective COX-2 inhibitor, parecoxib. The COX-2 protein level increased in wild-type mice in response to BUO and was not detectable in COX-2(-/-). COX-1 protein abundance was increased in sham-operated and BUO mice. Total AQP2 and -3 mRNA and protein levels decreased significantly after BUO in the cortex+outer medulla (C+OM) and inner medulla (IM). The decrease in C+OM AQP2 and -3 levels was attenuated/prevented in COX-2(-/-) mice, whereas there was no change in the IM. In parallel, inhibition of COX-2 by parecoxib rescued C+OM AQP3 and IM AQP2 protein level in wild-type mice subjected to BUO. In summary, 1) In C57BL/6 mice, ureteral obstruction increases renal COX-2 expression in interstitial cells and lowers AQP2/-3 abundance and 2) inhibition of COX-2 activity by targeted disruption or pharmacological blockade attenuates obstruction-induced AQP downregulation. In conclusion, COX-2-derived prostaglandins contribute to downregulation of transcellular water transporters in the collecting duct and likely to postobstruction diureses in the mouse.     

Metabolic and growth response of mink (Neovison vison) kits until 10 weeks of age when exposed to different dietary protein provision

Growth performance and metabolism were investigated in mink kits (n = 210) exposed to the same dietary treatment as their dams (n = 30), i.e. high (HP; 61% of metabolisable energy, ME), medium (MP; 48% of ME) or low (LP; 30% of ME) protein supply, from birth until 10 weeks of age. The kits were weighed weekly, and were measured by means of balance experiment and indirect calorimetry, in weeks eight and nine post-partum (p.p.). At weaning (seven weeks p.p.) and 10 weeks p.p. one kit per litter was killed and blood, liver and kidneys were collected. Plasma amino acid profiles, and hepatic abundance of mRNA for phosphoenolpyruvate carboxykinase (PEPCK), fructose 1,6-biphosphatase, pyruvate kinase and glucose-6-phosphatase (G-6-Pase) by q-PCR, were determined. There were no differences in live weights among kits the first four weeks of life when kits solely consumed milk, but male LP kits were the heaviest. After transition to solid feed MP kits weighed most at nine weeks of age (p < 0.05). At eight weeks of age, the kits fed the LP diet retained less (p < 0.05) N than HP and MP kits. Heat production did not differ among kits, although protein oxidation was higher (p < 0.001) in HP kits than in LP kits. Kits fed the LP diet had lower (p < 0.05) plasma concentrations of lysine, methionine and leucine than MP kits. Dietary treatment was not reflected in the relative abundance of any of the studied mRNAs, but kits had significantly lower abundance of all studied mRNA than their dams, ranging from 83% less PEPCK abundance to 40% less for G-6-Pase. The kidney mass was smallest (p < 0.01) in kits fed the LP diet, and liver masses were largest (p < 0.001) in HP kits. The results indicate that the LP diet did not meet the protein requirements for mink kits in the transition period from milk to solid feed. The capacity to regulate the rate of gluconeogenesis was even more limited in young mink kits than in adult dams. However, young mink kits can regulate protein oxidation in response to dietary protein supply, probably by adapting the size of the liver and kidneys to the level of protein supply.     

Association between FTO variant and change in body weight and its interaction with dietary factors: the DiOGenes study

Although FTO is an established obesity-susceptibility locus, it remains unknown whether it influences weight change in adult life and whether diet attenuates this association. Therefore, we investigated the association of FTO-rs9939609 with changes in weight and waist circumference (WC) during 6.8 years follow-up in a large-scale prospective study and examined whether these associations were modified by dietary energy percentage from fat, protein, carbohydrate, or glycemic index (GI). This study comprised data from five countries of European Prospective Investigation into Cancer and Nutrition (EPIC) and was designed as a case-cohort study for weight gain. Analyses included 11,091 individuals, of whom 5,584 were cases (age (SD), 47.6 (7.5) years), defined as those with the greatest unexplained annual weight gain during follow-up and 5,507 were noncases (48.0 (7.3) years), who were compared in our case-noncase (CNC) analyses. Furthermore, 6,566 individuals (47.9 (7.3) years) selected from the total sample (all noncases and 1,059 cases) formed the random subcohort (RSC), used for continuous trait analyses. Interactions were tested by including interaction terms in the models. In the RSC-analyses, FTO-rs9939609 was associated with BMI (β (SE), 0.17 (0.08) kg·m(-2)/allele; P = 0.034) and WC (0.47 (0.21) cm/allele; P = 0.026) at baseline, but not with weight change (5.55 (12.5) g·year(-1)/allele; P = 0.66) during follow up. In the CNC-analysis, FTO-rs9939609 was associated with increased risk of being a weight-gainer (OR: 1.1; P = 0.045). We observed no interaction between FTO-rs9939609 and dietary fat, protein and carbohydrate, and GI on BMI and WC at baseline or on change in weight and WC. FTO-rs9939609 is associated with BMI and WC at baseline, but association with weight gain is weak and only observed for extreme gain. Dietary factors did not influence the associations.     

Truncation of the Down syndrome candidate gene DYRK1A in two unrelated patients with microcephaly

We have identified and characterized two unrelated patients with prenatal onset of microcephaly, intrauterine growth retardation, feeding problems, developmental delay, and febrile seizures/epilepsy who both carry a de novo balanced translocation that truncates the DYRK1A gene at chromosome 21q22.2. DYRK1A belongs to the dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family, which is highly conserved throughout evolution. Given its localization in both the Down syndrome critical region and in the minimal region for partial monosomy 21, the gene has been studied intensively in animals and in humans, and DYRK1A has been proposed to be involved in the neurodevelopmental alterations associated with these syndromes. In the present study, we show that truncating mutations of DYRK1A result in a clinical phenotype including microcephaly.     

Long-term persistence of GM oilseed rape in the seedbank

Coexistence between genetically modified (GM) and non-GM plants is a field of rapid development and considerable controversy. In crops, it is increasingly important to understand and predict the GM volunteer emergence in subsequent non-GM crops. Theoretical models suggest recruitment from the seedbank over extended periods, but empirical evidence matching these predictions has been scarce. Here, we provide evidence of long-term GM seed persistence in conventional agriculture. Ten years after a trial of GM herbicide-tolerant oilseed rape, emergent seedlings were collected and tested for herbicide tolerance. Seedlings that survived the glufosinate herbicide (15 out of 38 volunteers) tested positive for at least one GM insert. The resulting density was equivalent to 0.01 plants m-2, despite complying with volunteer reduction recommendations. These results are important in relation to debating and regulating coexistence of GM and non-GM crops, particularly for planting non-GM crops after GM crops in the same field.     

The impact of elbow and knee joint lesions on abnormal gait and posture of sows

Background  

Joint lesions occur widespread in the Danish sow population and they are the most frequent cause for euthanasia. Clinically, it is generally impossible to differentiate between various types of non-inflammatory joint lesions. Consequently, it is often necessary to perform a post mortem examination in order to diagnose these lesions. A study was performed in order to examine the relation of abnormal gait and posture in sows with specific joint lesions, and thereby obtaining a clinical diagnostic tool, to be used by farmers and veterinarians for the evaluation of sows with joint problems.     

Effect of flecainide on atrial fibrillatory rate in a large animal model with induced atrial fibrillation

Background

Atrial fibrillatory cycle length has been considered one of the indices of atrial electrical remodelling during atrial fibrillation (AF), which can be assessed from surface ECG by computer-assisted calculation of atrial fibrillatory rate (AFR). Horses have been suggested as a bona fide model for AF studies since horses too, develop lone AF, however data on AF characteristics in horses are extremely sparse and non-invasive characterization of AF complexity using surface ECG processing has not been reported.

Aim

The aim was to study characteristics of induced AF and its modification by flecainide.

Methods

The study group consisted on 3 horses with spontaneous persistent AF and 13 with pace-induced AF. Seven horses were treated with saline (control) and eight with flecainide (2 mg/kg). ECGs were analysed using spatiotemporal cancellation of QRST complexes and calculation of AFR from the residual atrial signal.

Results

At AF onset, AFR was 295?±?52 fibrillations per minute (fpm) in the horses with induced AF treated with flecainide, 269?±?36 fpm in the control group (ns), and 364?±?26 fpm in the horses with spontaneous persistent AF (P?<?0.05 compared to the control group). Flecainide caused a decrease in AFR in all animals and restored sinus rhythm in the animals with induced AF. In the control animals, AFR increased from 269?±?36 fpm to a plateau of 313?±?14 fpm before decreasing to 288?±?28 fpm during the last 10% of the AF episodes preceding spontaneous conversion (P?<?0.05).

Conclusion

AFR in horses with induced AF resembles AFR in humans with paroxysmal AF. Flecainide caused a rapid decrease in AFR in all horses, further supporting the method to be a non-invasive technique to study the effect of antiarrhythmic compounds.