| 1. |
- Zhang, X., et al.
(författare)
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Human total, basal and activity energy expenditures are independent of ambient environmental temperature
- 2022
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Ingår i: iScience. - : Elsevier Inc.. - 2589-0042. ; 25:8
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Tidskriftsartikel (refereegranskat)abstract
- Lower ambient temperature (Ta) requires greater energy expenditure to sustain body temperature. However, effects of Ta on human energetics may be buffered by environmental modification and behavioral compensation. We used the IAEA DLW database for adults in the USA (n = 3213) to determine the effect of Ta (−10 to +30°C) on TEE, basal (BEE) and activity energy expenditure (AEE) and physical activity level (PAL). There were no significant relationships (p > 0.05) between maximum, minimum and average Ta and TEE, BEE, AEE and PAL. After adjustment for fat-free mass, fat mass and age, statistically significant (p < 0.01) relationships between TEE, BEE and Ta emerged in females but the effect sizes were not biologically meaningful. Temperatures inside buildings are regulated at 18–25°C independent of latitude. Hence, adults in the US modify their environments to keep TEE constant across a wide range of external ambient temperatures.
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| 2. |
- Speakman, John R., et al.
(författare)
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Total daily energy expenditure has declined over the past three decades due to declining basal expenditure, not reduced activity expenditure
- 2023
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Ingår i: Nature Metabolism. - : NATURE PORTFOLIO. - 2522-5812. ; 5:4, s. 579-588
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Obesity is caused by a prolonged positive energy balance(1,2). Whether reduced energy expenditure stemming from reduced activity levels contributes is debated(3,4). Here we show that in both sexes, total energy expenditure (TEE) adjusted for body composition and age declined since the late 1980s, while adjusted activity energy expenditure increased over time. We use the International Atomic Energy Agency Doubly Labelled Water database on energy expenditure of adults in the United States and Europe (n = 4,799) to explore patterns in total (TEE: n = 4,799), basal (BEE: n = 1,432) and physical activity energy expenditure (n = 1,432) over time. In males, adjusted BEE decreased significantly, but in females this did not reach significance. A larger dataset of basal metabolic rate (equivalent to BEE) measurements of 9,912 adults across 163 studies spanning 100 years replicates the decline in BEE in both sexes. We conclude that increasing obesity in the United States/Europe has probably not been fuelled by reduced physical activity leading to lowered TEE. We identify here a decline in adjusted BEE as a previously unrecognized factor.
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| 3. |
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| 4. |
- Dam, Veerle, et al.
(författare)
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Association of menopausal characteristics and risk of coronary heart disease : A pan-European case-cohort analysis
- 2019
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:4, s. 1275-1285
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Tidskriftsartikel (refereegranskat)abstract
- Background: Earlier age at menopause has been associated with increased risk of coronary heart disease (CHD), but the shape of association and role of established cardiovascular risk factors remain unclear. Therefore, we examined the associations between menopausal characteristics and CHD risk; the shape of the association between age at menopause and CHD risk; and the extent to which these associations are explained by established cardiovascular risk factors.Methods: We used data from EPIC-CVD, a case-cohort study, which includes data from 23 centres from 10 European countries. We included only women, of whom 10 880 comprise the randomly selected sub-cohort, supplemented with 4522 cases outside the sub-cohort. We conducted Prentice-weighted Cox proportional hazards regressions with age as the underlying time scale, stratified by country and adjusted for relevant confounders.Results: After confounder and intermediate adjustment, post-menopausal women were not at higher CHD risk compared with pre-menopausal women. Among post-menopausal women, earlier menopause was linearly associated with higher CHD risk [HRconfounder and intermediate adjusted per-year decrease = 1.02, 95% confidence interval (CI) = 1.01-1.03, p = 0.001]. Women with a surgical menopause were at higher risk of CHD compared with those with natural menopause (HRconfounder-adjusted = 1.25, 95% CI = 1.10-1.42, p < 0.001), but this attenuated after additional adjustment for age at menopause and intermediates (HR = 1.12, 95% CI = 0.96-1.29, p = 0.15). A proportion of the association was explained by cardiovascular risk factors.Conclusions: Earlier and surgical menopause were associated with higher CHD risk. These associations could partially be explained by differences in conventional cardiovascular risk factors. These women might benefit from close monitoring of cardiovascular risk factors and disease.
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| 5. |
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| 6. |
- Tolboom, N., et al.
(författare)
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The Dopamine Stabilizer (-)-OSU6162 Occupies a Subpopulation of Striatal Dopamine D2/D3 Receptors: An C-11 Raclopride PET Study in Healthy Human Subjects
- 2015
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Ingår i: Neuropsychopharmacology. - : Springer Science and Business Media LLC. - 0893-133X .- 1740-634X. ; 40:2, s. 472-479
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Tidskriftsartikel (refereegranskat)abstract
- (-)-OSU6162 is a dopamine stabilizer that can counteract both hyperdopaminergic and hypodopaminergic states. In this study, D2/D3 receptor occupancy of (-)-OSU6162 in the human brain was investigated using positron emission tomography (PET). Twelve male healthy volunteers underwent [C-11] raclopride PET scanning before and 1 h after a single oral dose of (-)-OSU6162 (15-90 mg). Blood samples for determination of (-)-OSU6162 and prolactin plasma levels were collected at T-max. Parametric images of [ 11 C] raclopride binding potential relative to nondisplaceable tissue (cerebellar grey matter) uptake (BPND) at baseline and after (-)-OSU6162 administration were generated using the simplified reference tissue model. MRI-based regions of interest were defined for the striatum, composed of caudate nucleus and putamen, and projected onto the co-registered parametric [C-11] raclopride BPND image. Furthermore, three striatal subregions, ie, anterior dorsal caudate, anterior dorsal putamen, and ventral striatum, were defined manually and additionally analyzed. Plasma concentrations of (-)-OSU6162, ranging from 0.01 to 0.9 mu M, showed a linear relationship with prolactin levels, reflecting blockade of pituitary D2 receptors. A concentration-dependent increase in striatal D2/D3 receptor occupancy was observed, reaching a value of about 20% at an (-)-OSU6162 plasma level of 0.2 mu M, and which for higher concentrations leveled off to a maximal occupancy of about 40%. Findings were similar in the striatal subregions. The present data corroborate the notion that (-)-OSU6162 binds preferentially to a subpopulation of D2/D3 receptors, possibly predominantly extrasynaptic, and this may form the basis for the dopamine-stabilizing properties of (-)-OSU6162.
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| 7. |
- Dam, Veerle, et al.
(författare)
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Genetically Determined Reproductive Aging and Coronary Heart Disease : A Bidirectional 2-sample Mendelian Randomization
- 2022
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 107:7, s. E2952-E2961
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Tidskriftsartikel (refereegranskat)abstract
- Background: Accelerated reproductive aging, in women indicated by early natural menopause, is associated with increased coronary heart disease (CHD) risk in observational studies. Conversely, an adverse CHD risk profile has been suggested to accelerate menopause. Objectives: To study the direction and evidence for causality of the relationship between reproductive aging and (non-)fatal CHD and CHD risk factors in a bidirectional Mendelian randomization (MR) approach, using age at natural menopause (ANM) genetic variants as a measure for genetically determined reproductive aging in women. We also studied the association of these variants with CHD risk (factors) in men. Design: Two-sample MR, using both cohort data as well as summary statistics, with 4 methods: simple and weighted median-based, standard inverse-variance weighted (IVW) regression, and MR-Egger regression. Participants: Data from EPIC-CVD and summary statistics from UK Biobank and publicly available genome-wide association studies were pooled for the different analyses. Main Outcome Measures: CHD, CHD risk factors, and ANM. Results: Across different methods of MR, no association was found between genetically determined reproductive aging and CHD risk in women (relative risk estimateIVW = 0.99; 95% confidence interval (CI), 0.97-1.01), or any of the CHD risk factors. Similarly, no associations were found in men. Neither did the reversed analyses show evidence for an association between CHD (risk factors) and reproductive aging. Conclusion: Genetically determined reproductive aging is not causally associated with CHD risk (factors) in women, nor were the genetic variants associated in men. We found no evidence for a reverse association in a combined sample of women and men.
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| 8. |
- Haftenberger, M, et al.
(författare)
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Physical activity of subjects aged 50-64 years involved in the European Prospective Investigation into Cancer and Nutrition (EPIC)
- 2002
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Ingår i: Public Health Nutrition. - 1475-2727. ; 5:6B, s. 1163-1177
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe physical activity of participants in the European Prospective Investigation into Cancer and Nutrition (EPIC). Design: A cross-sectional analysis of baseline data of a European prospective cohort study. Subjects: This analysis was restricted to participants in the age group 50-64 years, which was represented in all EPIC centres. It involved 236 386 participants from 25 centres in nine countries. In each EPIC centre, physical activity was assessed by standardised and validated questions. Frequency distribution of type of professional activity and participation in non-professional activities, and age-adjusted means, medians and percentiles of time dedicated to non-professional activities are presented for men and women from each centre. Results: Professional activity was most frequently classified as sedentary or standing in all centres. There was a wide variation regarding participation in different types of non-professional activities and time dedicated to these activities across EPIC centres. Over 80% of all EPIC participants engaged in walking, while less than 50% of the subjects participated in sport. Total time dedicated to recreational activities was highest among the Dutch participants and lowest among men from Malmo (Sweden) and women from Naples (Italy). In all centres, total time dedicated to recreational activity in the summer was higher than in the winter. Women from southern Europe spent the most time on housekeeping. Conclusions: There is a considerable variation of physical activity across EPIC centres. This variation was especially evident for recreational activities in both men and women.
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| 9. |
- van der Veldt, Astrid A M, et al.
(författare)
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Absolute Quantification of [11C]docetaxel Kinetics in Lung Cancer Patients Using Positron Emission Tomography
- 2011
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 17:14, s. 4814-4824
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Tidskriftsartikel (refereegranskat)abstract
- Purpose:Tumor resistance to docetaxel may be associated with reduced drug concentrations in tumor tissue. Positron emission tomography (PET) allows for quantification of radiolabeled docetaxel ([11C]docetaxel) kinetics and might be useful for predicting response to therapy. The primary objective was to evaluate the feasibility of quantitative [11C]docetaxel PET scans in lung cancer patients. The secondary objective was to investigate whether [11C]docetaxel kinetics were associated with tumor perfusion, tumor size, and dexamethasone administration.Experimental Design:Thirty-four lung cancer patients underwent dynamic PET–computed tomography (CT) scans using [11C]docetaxel. Blood flow was measured using oxygen-15 labeled water. The first 24 patients were premedicated with dexamethasone. For quantification of [11C]docetaxel kinetics, the optimal tracer kinetic model was developed and a noninvasive procedure was validated.Results:Reproducible quantification of [11C]docetaxel kinetics in tumors was possible using a noninvasive approach (image derived input function). Thirty-two lesions (size ≥4 cm3) were identified, having a variable net influx rate of [11C]docetaxel (range, 0.0023–0.0229 mL·cm−3·min−1). [11C]docetaxel uptake was highly related to tumor perfusion (Spearman's ρ = 0.815;P < 0.001), but not to tumor size (Spearman's ρ = −0.140; P = 0.446). Patients pretreated with dexamethasone showed lower [11C]docetaxel uptake in tumors (P = 0.013). Finally, in a subgroup of patients who subsequently received docetaxel therapy, relative high [11C]docetaxel uptake was related with improved tumor response.Conclusions:Quantification of [11C]docetaxel kinetics in lung cancer was feasible in a clinical setting. Variable [11C]docetaxel kinetics in tumors may reflect differential sensitivity to docetaxel therapy. Our findings warrant further studies investigating the predictive value of [11C]docetaxel uptake and the effects of comedication on [11C]docetaxel kinetics in tumors.
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| 10. |
- Coomans, Emma M., et al.
(författare)
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In vivo tau pathology is associated with synaptic loss and altered synaptic function
- 2021
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Ingår i: Alzheimer's Research and Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The mechanism of synaptic loss in Alzheimer’s disease is poorly understood and may be associated with tau pathology. In this combined positron emission tomography (PET) and magnetoencephalography (MEG) study, we aimed to investigate spatial associations between regional tau pathology ([18F]flortaucipir PET), synaptic density (synaptic vesicle 2A [11C]UCB-J PET) and synaptic function (MEG) in Alzheimer’s disease. Methods: Seven amyloid-positive Alzheimer’s disease subjects from the Amsterdam Dementia Cohort underwent dynamic 130-min [18F]flortaucipir PET, dynamic 60-min [11C]UCB-J PET with arterial sampling and 2 × 5-min resting-state MEG measurement. [18F]flortaucipir- and [11C]UCB-J-specific binding (binding potential, BPND) and MEG spectral measures (relative delta, theta and alpha power; broadband power; and peak frequency) were assessed in cortical brain regions of interest. Associations between regional [18F]flortaucipir BPND, [11C]UCB-J BPND and MEG spectral measures were assessed using Spearman correlations and generalized estimating equation models. Results: Across subjects, higher regional [18F]flortaucipir uptake was associated with lower [11C]UCB-J uptake. Within subjects, the association between [11C]UCB-J and [18F]flortaucipir depended on within-subject neocortical tau load; negative associations were observed when neocortical tau load was high, gradually changing into opposite patterns with decreasing neocortical tau burden. Both higher [18F]flortaucipir and lower [11C]UCB-J uptake were associated with altered synaptic function, indicative of slowing of oscillatory activity, most pronounced in the occipital lobe. Conclusions: These results indicate that in Alzheimer’s disease, tau pathology is closely associated with reduced synaptic density and synaptic dysfunction.
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