Physical activity is associated with a variety of health benefits, but the biological mechanisms that explain these associations remain unclear. Metabolomics is a powerful tool to comprehensively ...evaluate global metabolic signature associated with physical activity and helps to pinpoint the pathways that mediate the health effects of physical activity. There has been limited research on metabolomics and habitual physical activity, and no metabolomics study has examined sedentary behaviour and physical activity of different intensities.
In a group of Chinese adults (N = 277), we used an untargeted approach to examine 328 plasma metabolites in relation to accelerometer-measured physical activity, including overall volume of physical activity (physical activity energy expenditure (PAEE) and duration of physically active time) and sedentary time, and measures related to different intensities of physical activity (moderate-to-vigorous activity (MVPA), light activity, average physical activity intensity).
We identified 11 metabolites that were associated with total activity, with a false discovery rate of 0.2 or lower. Notably, we observed generally lower levels of amino acids in the valine, leucine and isoleucine metabolism pathway and of carbohydrates in sugar metabolism among participants with higher activity levels. Moreover, we found that PAEE, time spent in light activity and duration of physically active time were associated with a similar metabolic pattern, whereas the metabolic signature associated with sedentary time mirrored this pattern. In contrast, average activity intensity and time spent in MVPA appeared to be associated with somewhat different metabolic patterns.
Overall, the metabolomics patterns support a beneficial role of higher volume of physical activity in cardiometabolic health. Our findings identified candidate pathways and provide insight into the mechanisms underlying the health effects of physical activity.
Metabolomic analysis of feces may provide insights on colorectal cancer (CRC) if assay performance is satisfactory. In lyophilized feces from 48 CRC cases, 102 matched controls, and 48 masked quality ...control specimens, 1043 small molecules were detected with a commercial platform. Assay reproducibility was good for 527 metabolites technical intraclass correlation coefficient (ICC) >0.7 in quality control specimens, but reproducibility in 6-month paired specimens was lower for the majority of metabolites (within-subject ICC ≤0.5). In the CRC cases and controls, significant differences (false discovery rate ≤0.10) were found for 41 of 1043 fecal metabolites. Direct cancer association was found with three fecal heme-related molecules covariate-adjusted 90th versus 10th percentile odds ratio (OR) = 17-345, 18 peptides/amino acids (OR = 3-14), palmitoyl-sphingomyelin (OR = 14), mandelate (OR = 3) and p-hydroxy-benzaldehyde (OR = 4). Conversely, cancer association was inverse with acetaminophen metabolites (OR <0.1), tocopherols (OR = 0.3), sitostanol (OR = 0.2), 3-dehydrocarnitine (OR = 0.4), pterin (OR = 0.3), conjugated-linoleate-18-2N7 (OR = 0.2), N-2-furoyl-glycine (OR = 0.3) and p-aminobenzoate (PABA, OR = 0.2). Correlations suggested an independent role for palmitoyl-sphingomyelin and a central role for PABA (which was stable over 6 months, within-subject ICC 0.67) modulated by p-hydroxy-benzaldehyde. Power calculations based on ICCs indicate that only 45% of metabolites with a true relative risk 5.0 would be found in prospectively collected, prediagnostic specimens from 500 cases and 500 controls. Thus, because fecal metabolites vary over time, very large studies will be needed to reliably detect associations of many metabolites that potentially contribute to CRC.
Encapsulation of actives comprises an area of exploration undergoing rapid growth in both academic and industrial research settings. Encapsulation processes are employed as a part of product ...synthesis processes for improved efficiency, enhanced stability, active ingredient compatibility, increased safety, targeted delivery, and novel performance of the end product. Such technical benefits enable producers to offer products with increased formulation complexity, access new markets, differentiate products, and improve compatibility and stability, while meeting consumer demands with improved performance, reduced costs, and new actives. In this review, we highlight several emerging academic areas of encapsulation that we believe have specific relevance to industrial formulation, with a focus on three primary areas: supramolecular encapsulation, aqueous self-assembled systems, and emulsion-based capsules. The goal of this review is to help identify the major challenges facing encapsulation technology adoption in the chemical industry, bringing focus and maximizing the potential value of ongoing research efforts.
Modern biomedical and epidemiological studies often measure hundreds or thousands of biomarkers, such as gene expression or metabolite levels. Although there is an extensive statistical literature on ...adjusting for 'multiple comparisons' when testing whether these biomarkers are directly associated with a disease, testing whether they are biological mediators between a known risk factor and a disease requires a more complex null hypothesis, thus offering additional methodological challenges.
We propose a permutation approach that tests multiple putative mediators and controls the family wise error rate. We demonstrate that, unlike when testing direct associations, replacing the Bonferroni correction with a permutation approach that focuses on the maximum of the test statistics can significantly improve the power to detect mediators even when all biomarkers are independent. Through simulations, we show the power of our method is 2-5× larger than the power achieved by Bonferroni correction. Finally, we apply our permutation test to a case-control study of dietary risk factors and colorectal adenoma to show that, of 149 test metabolites, docosahexaenoate is a possible mediator between fish consumption and decreased colorectal adenoma risk.
R-package included in online Supplementary Material.
Metabolite levels within an individual vary over time. This within-individual variability, coupled with technical variability, reduces the power for epidemiologic studies to detect associations with ...disease. Here, the authors assess the variability of a large subset of metabolites and evaluate the implications for epidemiologic studies.
Using liquid chromatography/mass spectrometry (LC/MS) and gas chromatography-mass spectroscopy (GC/MS) platforms, 385 metabolites were measured in 60 women at baseline and year-one of the Shanghai Physical Activity Study, and observed patterns were confirmed in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening study.
Although the authors found high technical reliability (median intraclass correlation = 0.8), reliability over time within an individual was low. Taken together, variability in the assay and variability within the individual accounted for the majority of variability for 64% of metabolites. Given this, a metabolite would need, on average, a relative risk of 3 (comparing upper and lower quartiles of "usual" levels) or 2 (comparing quartiles of observed levels) to be detected in 38%, 74%, and 97% of studies including 500, 1,000, and 5,000 individuals. Age, gender, and fasting status factors, which are often of less interest in epidemiologic studies, were associated with 30%, 67%, and 34% of metabolites, respectively, but the associations were weak and explained only a small proportion of the total metabolite variability.
Metabolomics will require large, but feasible, sample sizes to detect the moderate effect sizes typical for epidemiologic studies.
We offer guidelines for determining the sample sizes needed to conduct metabolomic studies in epidemiology.
The history of the Arctic Ocean during the Cenozoic era (0-65 million years ago) is largely unknown from direct evidence. Here we present a Cenozoic palaeoceanographic record constructed from >400 m ...of sediment core from a recent drilling expedition to the Lomonosov ridge in the Arctic Ocean. Our record shows a palaeoenvironmental transition from a warm 'greenhouse' world, during the late Palaeocene and early Eocene epochs, to a colder 'icehouse' world influenced by sea ice and icebergs from the middle Eocene epoch to the present. For the most recent approximately 14 Myr, we find sedimentation rates of 1-2 cm per thousand years, in stark contrast to the substantially lower rates proposed in earlier studies; this record of the Neogene reveals cooling of the Arctic that was synchronous with the expansion of Greenland ice (approximately 3.2 Myr ago) and East Antarctic ice (approximately 14 Myr ago). We find evidence for the first occurrence of ice-rafted debris in the middle Eocene epoch (approximately 45 Myr ago), some 35 Myr earlier than previously thought; fresh surface waters were present at approximately 49 Myr ago, before the onset of ice-rafted debris. Also, the temperatures of surface waters during the Palaeocene/Eocene thermal maximum (approximately 55 Myr ago) appear to have been substantially warmer than previously estimated. The revised timing of the earliest Arctic cooling events coincides with those from Antarctica, supporting arguments for bipolar symmetry in climate change.
The average age at menarche declined in European and U.S. populations during the 19th and 20th centuries. The timing of pubertal events may have broad implications for chronic disease risks in aging ...women. Here we tested for associations of recalled menarcheal age with risks of 19 cancers in 536,450 women median age, 60 years (range, 31-39 years) in nine prospective U.S. and European cohorts that enrolled participants from 1981 to 1998. Cox regression estimated multivariable-adjusted HRs and 95% confidence intervals (CI) for associations of the age at menarche with risk of each cancer in each cohort and random-effects meta-analysis was used to generate summary estimates for each cancer. Over a median 10 years of follow-up, 60,968 women were diagnosed with a first primary incident cancer. Inverse linear associations were observed for seven of 19 cancers studied. Each additional year in the age at menarche was associated with reduced risks of endometrial cancer (HR = 0.91; 95% CI, 0.89-0.94), liver cancer (HR = 0.92; 95% CI, 0.85-0.99), melanoma (HR = 0.95; 95% CI, 0.93-0.98), bladder cancer (HR = 0.96; 95% CI, 0.93-0.99), and cancers of the colon (HR = 0.97; 95% CI, 0.96-0.99), lung (HR = 0.98; 95% CI, 0.96-0.99), and breast (HR = 0.98; 95% CI, 0.93-0.99). All but one of these associations remained statistically significant following adjustment for baseline body mass index. Similarities in the observed associations between menarche and seven cancers suggest shared underlying causes rooted early in life. We propose as a testable hypothesis that early exposure to sex hormones increases mid-life cancer risks by altering functional capacities of stem cells with roles in systemic energy balance and tissue homeostasis. SIGNIFICANCE: Age at menarche is associated with risk for seven cancers in middle-aged women, and understanding the shared underlying causal pathways across these cancers may suggest new avenues for cancer prevention.
Group testing in mediation analysis Derkach, Andriy; Moore, Steven C.; Boca, Simina M. ...
Statistics in medicine,
15 August 2020, Letnik:
39, Številka:
18
Journal Article
Recenzirano
Odprti dostop
We consider the scenario where there is an exposure, multiple biologically defined sets of biomarkers, and an outcome. We propose a new two‐step procedure that tests if any of the sets of biomarkers ...mediate the exposure/outcome relationship, while maintaining a prespecified familywise error rate. The first step of the proposed procedure is a screening step that removes all groups that are unlikely to be strongly associated with both the exposure and the outcome. The second step adapts recent advances in postselection inference to test if there are true mediators in each of the remaining candidate sets. We use simulation to show that this simple two‐step procedure has higher statistical power to detect true mediating sets when compared with existing procedures. We then use our two‐step procedure to identify a set of Lysine‐related metabolites that potentially mediate the known relationship between increased body mass index and the increased risk of estrogen‐receptor positive breast cancer in postmenopausal women.
Limited evidence suggests that adiposity and lack of physical activity may increase the risk of chronic obstructive pulmonary disease (COPD). We investigated the relation of body size and physical ...activity with incidence of COPD.
We obtained data on anthropometric measurements and physical activity from 113,279 participants in the National Institutes of Health-AARP Diet and Health Study who reported no diagnosis of COPD at baseline (1995-1996). We estimated associations between these measurements and subsequent diagnosis of COPD between 1996 and 2006, with extensive adjustment for smoking and other potentially confounding variables.
Participants reported 3648 new COPD diagnoses during follow-up. The incidence of COPD was higher in both severely obese (body mass index BMI ≥ 35) and underweight (BMI < 18.5) participants, but after adjustment for waist circumference, only underweight remained positively associated with COPD (relative risk RR 1.56, 95% confidence interval CI 1.15-2.11). Larger waist circumference (highest v. normal categories, adjusted RR 1.72, 95% CI 1.37-2.16) and higher waist-hip ratio (highest v. normal categories, adjusted RR 1.46, 95% CI 1.23-1.73) were also positively associated with COPD. In contrast, hip circumference (highest v. normal categories, adjusted RR 0.78, 95% CI 0.62-0.98) and physical activity (≥ 5 v. 0 times/wk, adjusted RR 0.71, 95% CI 0.63-0.79) were inversely associated with COPD.
Obesity, in particular abdominal adiposity, was associated with an increased risk of COPD, and increased hip circumference and physical activity were associated with a decreased risk of COPD. These findings suggest that following guidelines for a healthy body weight, body shape and physical activity decrease the risk of COPD.
Epidemiologic studies examining circulating levels of inflammatory markers in relation to obesity and physical inactivity may aid in our understanding of the role of inflammation in obesity-related ...cancers. However, previous studies on this topic have focused on a limited set of markers.
We evaluated associations between body mass index (BMI) and vigorous physical activity level, based on self-report, and serum levels of 78 inflammation-related markers. Markers were measured using a bead-based multiplex method among 1,703 men and women, ages 55-74 years, and with no prior history of cancer at blood draw, and selected for case-control studies nested within the Prostate, Lung, Ovarian, and Colorectal Cancer Screening Trial. Analyses were adjusted for age, sex, smoking, case-control study, physical activity, and BMI.
Twelve markers were positively associated with BMI after FDR correction. ORs and 95% confidence interval (CI) for highest versus lowest levels of CCL2/MCP-1, CXCL5/ENA-78, sTNFRII, CXCL10/IP-10, CXCL6/GCP2, CCL13/MCP-4, amylin, CRP, C-peptide, CCL19/MIP-3b, insulin, and leptin were: 1.50 (1.14-1.98), 1.52 (1.12-2.05), 1.61 (1.17-2.20), 1.69 (1.25-2.28), 1.74 (1.24-2.44), 1.75 (1.22-2.50), 1.91 (1.31-2.78), 2.41 (1.36-4.25), 2.78 (1.83-4.24), 3.30 (2.28-4.78), 4.05 (2.51-6.55), and 50.03 (19.87-125.99) per 5 kg/m(2), respectively. Only CXCL12/SDF-1a was associated with physical activity (≥3 vs. <1 h/wk; OR, 3.28; 95% CI, 1.55-6.94) after FDR correction.
BMI was associated with a wide range of circulating markers involved in the inflammatory response.
This cross-sectional analysis identified serum markers could be considered in future studies aimed at understanding the underlying mechanisms linking inflammation with obesity and obesity-related cancers.
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