The relation between sleep duration and sedentary behaviours in European adults.

Too much sitting, and both short and long sleep duration are associated with obesity, but little is known on the nature of the relations between these behaviours. We therefore examined the associations between sleep duration and time spent sitting in adults across five urban regions in Europe. We used cross-sectional survey data from 6,037 adults (mean age 51.9 years (SD 16.4), 44.0% men) to assess the association between self-reported short (8 h per night) sleep duration with self-report total time spent sitting, time spent sitting at work, during transport, during leisure and while watching screens. The multivariable multilevel linear regression models were tested for moderation by urban region, age, gender, education and weight status. Because short sleepers have more awake time to be sedentary, we also used the percentage of awake time spent sedentary as an outcome. Short sleepers had 26.5 min day(-1) more sedentary screen time, compared with normal sleepers (CI 5.2; 47.8). No statistically significant associations were found with total or other domains of sedentary behaviour, and there was no evidence for effect modification. Long sleepers spent 3.2% higher proportion of their awake time sedentary compared with normal sleepers. Shorter sleep was associated with increased screen time in a sample of European adults, irrespective of urban region, gender, age, educational level and weight status. Experimental studies are needed to assess the prospective relation between sedentary (screen) time and sleep duration

Heterogeneity in glucose response curves during an oral glucose tolerance test and associated cardiometabolic risk

We aimed to examine heterogeneity in glucose response curves during an oral glucose tolerance test with multiple measurements and to compare cardiometabolic risk profiles between identified glucose response curve groups. We analyzed data from 1,267 individuals without diabetes from five studies in Denmark, the Netherlands and the USA. Each study included between 5 and 11 measurements at different time points during a 2-h oral glucose tolerance test, resulting in 9,602 plasma glucose measurements. Latent class trajectories with a cubic specification for time were fitted to identify different patterns of plasma glucose change during the oral glucose tolerance test. Cardiometabolic risk factor profiles were compared between the identified groups. Using latent class trajectory analysis, five glucose response curves were identified. Despite similar fasting and 2-h values, glucose peaks and peak times varied greatly between groups, ranging from 7-12 mmol/L, and 35-70 min. The group with the lowest and earliest plasma glucose peak had the lowest estimated cardiovascular risk, while the group with the most delayed plasma glucose peak and the highest 2-h value had the highest estimated risk. One group, with normal fasting and 2-h values, exhibited an unusual profile, with the highest glucose peak and the highest proportion of smokers and men. The heterogeneity in glucose response curves and the distinct cardiometabolic risk profiles may reflect different underlying physiologies. Our results warrant more detailed studies to identify the source of the heterogeneity across the different phenotypes and whether these differences play a role in the development of type 2 diabetes and cardiovascular disease

A single site in human β-hexosaminidase A binds both 6-sulfate-groups on hexosamines and the sialic acid moiety of GM2 ganglioside

AbstractHuman β-hexosaminidase A (Hex A) (αβ) is composed of two subunits whose primary structures are ∼60% identical. Deficiency of either subunit results in severe neurological disease due to the storage of GM2 ganglioside; Tay–Sachs disease, α deficiency, and Sandhoff disease, β deficiency. Whereas both subunits contain active sites only the α-site can efficiently bind negatively charged 6-sulfated hexosamine substrates and GM2 ganglioside. We have recently identified the αArg424 as playing a critical role in the binding of 6-sulfate-containing substrates, and βAsp452 as actively inhibiting their binding. To determine if these same residues affect the binding of the sialic acid moiety of GM2 ganglioside, an αArg424Gln form of Hex A was expressed and its kinetics analyzed using the GM2 activator protein:[3H]-GM2 ganglioside complex as a substrate. The mutant showed a ∼3-fold increase in its Km for the complex. Next a form of Hex B (ββ) containing a double mutation, βAspLeu453AsnArg (duplicating the α-aligning sequences), was expressed. As compared to the wild type (WT), the mutant exhibited a >30-fold increase in its ability to hydrolyze a 6-sulfated substrate and was now able to hydrolyze GM2 ganglioside when the GM2 activator protein was replaced by sodium taurocholate. Thus, this α-site is critical for binding both types of negatively charge substrates

Naturally occurring circadian rhythm and sleep duration are related to executive functions in early adulthood

Experimental sleep deprivation studies suggest that insufficient sleep and circadian misalignment associates with poorer executive function. It is not known whether this association translates to naturally occurring sleep patterns. A total of 512 of full-term-born members of the Arvo Ylppö Longitudinal Study [mean age = 25.3, standard deviation (SD) = 0.65] (44.3% men) wore actigraphs to define sleep duration, its irregularity and circadian rhythm (sleep mid-point) during a 1-week period (mean 6.9 nights, SD = 1.7). Performance-based executive function was assessed with the Trail-Making Test, Conners’ Continuous Performance Test and Stroop. The self-rated adult version of Behavior Rating Inventory of Executive Function was used to assess trait-like executive function. We found that performance-based and self-reported trait-like executive function correlated only modestly (all correlations ≤0.17). Shorter sleep duration associated with more commission errors. Later circadian rhythm associated with poorer trait-like executive function, as indicated by the Brief Metacognitive Index and the Behavior Regulation Index. Those belonging to the group with the most irregular sleep duration performed slower than others in the Trail-Making Test Part A. All associations were adjusted for sex, age, socioeconomic status and body mass index. In conclusion, naturally occurring insufficient sleep and later circadian rhythm showed modest associations with poorer executive function. Shorter habitual sleep duration was associated with lower scores of performance-based tests of executive function, and later circadian rhythm was associated mainly with poorer trait-like executive function characteristics. Our findings suggest additionally that sleep duration and circadian rhythm associate with different domains of executive function, and there are no additive effects between the two

Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration

Background & Aims: Excess liver iron content is common and is linked to hepatic and extrahepatic disease risk. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases. Methods: First, we performed a genome-wide association study (GWAS) in 8,289 individuals in UK Biobank with MRI quantified liver iron, and validated our findings in an independent cohort (n=1,513 from IMI DIRECT). Second, we used Mendelian randomisation to test the causal effects of 29 predominantly metabolic traits on liver iron content. Third, we tested phenome-wide associations between liver iron variants and 770 anthropometric traits and diseases. Results: We identified three independent genetic variants (rs1800562 (C282Y) and rs1799945 (H63D) in HFE and rs855791 (V736A) in TMPRSS6) associated with liver iron content that reached the GWAS significance threshold (p<5x10-8). The two HFE variants account for ~85% of all cases of hereditary haemochromatosis. Mendelian randomisation analysis provided evidence that higher central obesity plays a causal role in increased liver iron content. Phenome-wide association analysis demonstrated shared aetiopathogenic mechanisms for elevated liver iron, high blood pressure, cirrhosis, malignancies, neuropsychiatric and rheumatological conditions, while also highlighting inverse associations with anaemias, lipidaemias and ischaemic heart disease. Conclusion: Our study provides genetic evidence that mechanisms underlying higher liver iron content are likely systemic rather than organ specific, that higher central obesity is causally associated with higher liver iron, and that liver iron shares common aetiology with multiple metabolic and non-metabolic diseases

Acute hunger modifies responses on the Three Factor Eating Questionnaire hunger and disinhibition, but not restraint, scales

It is widely assumed that responses on the Three Factor Eating Questionnaire (TFEQ) represent long-term (trait) attitudes to eating behaviour. However, the questionnaire requires agreement with a number of food related statements, and it is possible that some are easier to agree with when assessed hungry than sated. To test this potential state-dependency, participants completed a 100 mm visual analogue scale rating of their current hunger at the time they completed the TFEQ. Data were collected from two cohorts: Cohort 1 (507 women and 119 men) completed both measures on paper, while the hunger rating was computerised in Cohort 2 (179 women). Regression analysis revealed significant effects of rated hunger on scores on the hunger (TFEQ-H) and disinhibition (TFEQ-D) but not restraint (TFEQ-R) subscales, with higher TFEQ-H and TFEQ-D scores when participants were more hungry. In addition, 61 women and two men from Cohort 1 completed the measures on two separate occasions. Here, scores on TFEQ-H were higher on days when these participants were hungrier, but no differences in TFEQ-D or TFEQ-R were found. Overall these data suggest TFEQ-H could be interpreted as an indirect measure of current hunger, that scores on TFEQ-D are partly moderated by hunger but TFEQ-R is a more trait-like measure of restraint

The mediating role of comorbid conditions in the association between type 2 diabetes and cognition: a cross-sectional observational study using the UK Biobank cohort

Aims: Using the UK Biobank cohort, a large sample of middle aged and older adults in the UK, the present study aimed to examine the cross-sectional association between type 2 diabetes and cognition and to assess the hypothesised mediating role of common comorbid conditions, whilst controlling for important demographic and lifestyle factors. Methods: Using regression models and general structural equation models, we examined the cross-sectional association between type 2 diabetes status and: fluid intelligence; reaction time; visual memory; digit span and prospective memory; and the hypothesised mediating role of common comorbid conditions: visceral obesity; sleep problems; macrovascular problems; respiratory problems,; cancer and depressive symptoms in 47,468 participants from the UK Biobank cohort, of whom 1,831 have type 2 diabetes. We controlled for ethnicity, sex, age, deprivation, smoking status, alcohol consumption, physical activity levels and use of diabetes medication. Results: Participants with type 2 diabetes had a significantly shorter digit span, b = -0.14, 99.2% CIs [-0.27, -0.11] than those without type 2 diabetes. Those with type 2 diabetes did not differ from those without type 2 diabetes on fluid intelligence, reaction time, visual memory and prospective memory. The associations that do exist between type 2 diabetes and cognition are consistently mediated via macrovascular problems, depressive symptoms, and to a lesser extent visceral obesity. Respiratory problems, sleep disturbances and cancer did not mediate the association between type 2 diabetes status and measures of cognition. Conclusions: Comorbid conditions explain some of the observed association between type 2 diabetes and cognitive deficits. This suggests that prevention, management or treatment of these comorbid conditions may be important to reduce the likelihood of cognitive decline. Treatment studies with long follow-ups are needed to examine this. Tweet: Comorbid conditions explain the association between type 2 diabetes and cognitive deficits. Prevention, management or treatment of these comorbid conditions may prevent or delay the onset of cognitive decline in people with type 2 diabetes

Three-dimensional cometary dust coma modelling in the collisionless regime: strengths and weaknesses

Inverse coma and tail modelling of comets based on the method developed by Finson & Probstein is commonly used to analyse cometary coma images. Models of this type often contain a large number of assumptions that may not be constrained unless wide temporal or spectral coverage is available and the comets are bright and at relatively small geocentric distance. They are used to predict physical parameters, such as the mass distribution of the dust, but rarely give assessments of the accuracy of the estimate. A three-dimensional cometary dust coma model in the collisionless regime has been developed to allow the effectiveness of such models to constrain dust coma properties to be tested. The model is capable of simulating the coma morphology for the following input parameters: the comet nucleus shape, size, rotation, emission function (including active fraction and jets), grain velocity distribution (and dispersion), size distribution, dust production rate, grain material and light scattering from the cometary dust. Characterization of the model demonstrates that the mass distribution cannot be well constrained as is often assumed; the cumulative mass distribution index ? can only be constrained to within ±0.15. The model is highly sensitive to the input grain terminal velocity distribution so model input can be tested with a large degree of confidence. Complex secondary parameters such as jets, rotation and grain composition all have an effect on the structure of the coma in similar ways, so unique solutions for these parameters cannot be derived from a single optical image alone. Multiple images at a variety of geometries close in time can help constrain these effects. The model has been applied to photometric observations of comets 126P/IRAS and 46P/Wirtanen to constrain a number of physical properties including the dust production rate and mass distribution index. The derived dust production rate (Qdust) for 46P/Wirtanen was 3+7/1.5 kg s1 at a pre-perihelion heliocentric distance of 1.8 au, and for P/IRAS was 50+100/20 kg s1 at a pre-perihelion heliocentric distance of 1.7 au; both comets exhibited a mass distribution index ? = 0.8 ± 0.15

Poor sleep quality at baseline is associated with increased aggression over one year in forensic psychiatric patients

Objective: In forensic psychiatric patients, sleep problems as well as impulsivity and aggression are highly prevalent, yet studies on their association over time are lacking. This study investigates the association between sleep quality and changes in impulsivity and aggression in forensic psychiatric patients over one year. Methods: Data were drawn from an ongoing prospective observational study in adult forensic psychiatric patients admitted to a forensic treatment facility between October 2006 and January 2018. Validated self-reports and observational instruments were used to assess sleep quality, impulsivity and aggression upon admission to the hospital and after one year. Linear regression analyses were performed to examine the association between sleep quality, impulsivity and aggression. All models were adjusted for baseline values of outcome measures, demographic features and general psychopathology. Results: Data from 83 men (age 37.7 ± 11.7 years) with completed consecutive measurements were analyzed. Poor sleep quality was associated with increased self-reported aggression (β = 1.08; 95% CI, 0.38–1.78). This association was positively confounded by general psychopathology, indicating that sleep quality is specifically related to self-reported aggression instead of being part of general psychopathology (adjusted β = 1.18; 95% CI, 0.39–1.97). Poor sleep quality was not associated with changes in self-reported impulsivity, clinician-rated impulsivity or clinician-rated hostility in this population. Conclusion: Poor sleep quality was associated with an increase in self-reported aggression over one year in male forensic psychiatric patients. Early evaluation and treatment of sleep problems in (forensic) psychiatric patients may play an important role in reducing the risk of aggressive behavior

Dietary restraint and control over "wanting" following consumption of "forbidden" food.

Eating behavior can be influenced by the rewarding value of food, i.e., "liking" and "wanting." The objective of this study was to assess in normal-weight dietary restrained (NR) vs. unrestrained (NU) eaters how rewarding value of food is affected by satiety, and by eating a nonhealthy perceived, dessert-specific food vs. a healthy perceived, neutral food (chocolate mousse vs. cottage cheese). Subjects (24NR age = 25.0 +/- 8.2 years, BMI = 22.3 +/- 2.1 kg/m(2); 26NU age = 24.8 +/- 8.0 years, BMI = 22.1 +/- 1.7 kg/m(2)) came to the university twice, fasted (randomized crossover design). Per test-session "liking" and "wanting" for 72 items divided in six categories (bread, filling, drinks, dessert, sweets, stationery (placebo)) was measured, before and after consumption of chocolate mousse/cottage cheese, matched for energy content (5.6 kJ/g) and individual daily energy requirements (10%). Chocolate mousse was liked more than cottage cheese (P < 0.05). After consumption of chocolate mousse or cottage cheese, appetite and "liking" vs. placebo were decreased in NR and NU (P < 0.03), whereas "wanting" was only decreased in NR vs. NU (P </= 0.01). In NR vs. NU "wanting" was specifically decreased after chocolate mousse vs. cottage cheese; this decrease concerned especially "wanting" for bread and filling (P < 0.05). To conclude, despite similar decreases in appetite and "liking" after a meal in NR and NU, NR decrease "wanting" in contrast to NU. NR decrease "wanting" specifically for a nonhealthy perceived, "delicious," dessert-specific food vs. a nutritional identical, yet healthy perceived, slightly less "delicious," "neutral" food. A healthy perceived food may thus impose greater risk for control of energy intake in NR