| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
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| 3. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 4. |
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| 5. |
- Bigdeli, TB, et al.
(författare)
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Genetic effects influencing risk for major depressive disorder in China and Europe
- 2017
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 7:3, s. e1074-
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Tidskriftsartikel (refereegranskat)abstract
- Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30–40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects. We determined the fraction of SNPs displaying consistent directions of effect, assessed the significance of polygenic risk scores and estimated the genetic correlation of MDD across ancestries. Subsequent trans-ancestry meta-analyses combined SNP-level evidence of association. Sign tests and polygenic score profiling weakly support an overlap of SNP effects between East Asian and European populations. We estimated the trans-ancestry genetic correlation of lifetime MDD as 0.33; female-only and recurrent MDD yielded estimates of 0.40 and 0.41, respectively. Common variants downstream of GPHN achieved genome-wide significance by Bayesian trans-ancestry meta-analysis (rs9323497; log10 Bayes Factor=8.08) but failed to replicate in an independent European sample (P=0.911). Gene-set enrichment analyses indicate enrichment of genes involved in neuronal development and axonal trafficking. We successfully demonstrate a partially shared polygenic basis of MDD in East Asian and European populations. Taken together, these findings support a complex etiology for MDD and possible population differences in predisposing genetic factors, with important implications for future genetic studies.
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| 6. |
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| 7. |
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| 8. |
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| 9. |
- Bais, A. F., et al.
(författare)
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Environmental effects of ozone depletion, UV radiation and interactions with climate change: UNEP Environmental Effects Assessment Panel, update 2017
- 2018
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Ingår i: Photochemical & Photobiological Sciences. - : Springer Science and Business Media LLC. - 1474-905X .- 1474-9092. ; 17:2, s. 127-179
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Tidskriftsartikel (refereegranskat)abstract
- The Environmental Effects Assessment Panel (EEAP) is one of three Panels of experts that inform the Parties to the Montreal Protocol. The EEAP focuses on the effects of UV radiation on human health, terrestrial and aquatic ecosystems, air quality, and materials, as well as on the interactive effects of UV radiation and global climate change. When considering the effects of climate change, it has become clear that processes resulting in changes in stratospheric ozone are more complex than previously held. Because of the Montreal Protocol, there are now indications of the beginnings of a recovery of stratospheric ozone, although the time required to reach levels like those before the 1960s is still uncertain, particularly as the effects of stratospheric ozone on climate change and vice versa, are not yet fully understood. Some regions will likely receive enhanced levels of UV radiation, while other areas will likely experience a reduction in UV radiation as ozone- and climate-driven changes affect the amounts of UV radiation reaching the Earth's surface. Like the other Panels, the EEAP produces detailed Quadrennial Reports every four years; the most recent was published as a series of seven papers in 2015 (Photochem. Photobiol. Sci., 2015, 14, 1-184). In the years in between, the EEAP produces less detailed and shorter Update Reports of recent and relevant scientific findings. The most recent of these was for 2016 (Photochem. Photobiol. Sci., 2017, 16, 107-145). The present 2017 Update Report assesses some of the highlights and new insights about the interactive nature of the direct and indirect effects of UV radiation, atmospheric processes, and climate change. A full 2018 Quadrennial Assessment, will be made available in 2018/2019.
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| 10. |
- de Gonzalez, Amy Berrington, et al.
(författare)
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Body-Mass Index and Mortality among 1.46 Million White Adults.
- 2010
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Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 363:23, s. 2211-2219
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Tidskriftsartikel (refereegranskat)abstract
- Background: A high body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) is associated with increased mortality from cardiovascular disease and certain cancers, but the precise relationship between BMI and all-cause mortality remains uncertain. Methods: We used Cox regression to estimate hazard ratios and 95% confidence intervals for an association between BMI and all-cause mortality, adjusting for age, study, physical activity, alcohol consumption, education, and marital status in pooled data from 19 prospective studies encompassing 1.46 million white adults, 19 to 84 years of age (median, 58). Results: The median baseline BMI was 26.2. During a median follow-up period of 10 years (range, 5 to 28), 160,087 deaths were identified. Among healthy participants who never smoked, there was a J-shaped relationship between BMI and all-cause mortality. With a BMI of 22.5 to 24.9 as the reference category, hazard ratios among women were 1.47 (95 percent confidence interval [CI], 1.33 to 1.62) for a BMI of 15.0 to 18.4; 1.14 (95% CI, 1.07 to 1.22) for a BMI of 18.5 to 19.9; 1.00 (95% CI, 0.96 to 1.04) for a BMI of 20.0 to 22.4; 1.13 (95% CI, 1.09 to 1.17) for a BMI of 25.0 to 29.9; 1.44 (95% CI, 1.38 to 1.50) for a BMI of 30.0 to 34.9; 1.88 (95% CI, 1.77 to 2.00) for a BMI of 35.0 to 39.9; and 2.51 (95% CI, 2.30 to 2.73) for a BMI of 40.0 to 49.9. In general, the hazard ratios for the men were similar. Hazard ratios for a BMI below 20.0 were attenuated with longer-term follow-up. Conclusions: In white adults, overweight and obesity (and possibly underweight) are associated with increased all-cause mortality. All-cause mortality is generally lowest with a BMI of 20.0 to 24.9. N Engl J Med 2010;363:2211-9.
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| 11. |
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| 12. |
- Barnes, Paul W., et al.
(författare)
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Ozone depletion, ultraviolet radiation, climate change and prospects for a sustainable future
- 2019
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Ingår i: Nature Sustainability. - : Springer Science and Business Media LLC. - 2398-9629. ; 2:7, s. 569-579
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Forskningsöversikt (refereegranskat)abstract
- © 2019, Springer Nature Limited. Changes in stratospheric ozone and climate over the past 40-plus years have altered the solar ultraviolet (UV) radiation conditions at the Earth’s surface. Ozone depletion has also contributed to climate change across the Southern Hemisphere. These changes are interacting in complex ways to affect human health, food and water security, and ecosystem services. Many adverse effects of high UV exposure have been avoided thanks to the Montreal Protocol with its Amendments and Adjustments, which have effectively controlled the production and use of ozone-depleting substances. This international treaty has also played an important role in mitigating climate change. Climate change is modifying UV exposure and affecting how people and ecosystems respond to UV; these effects will become more pronounced in the future. The interactions between stratospheric ozone, climate and UV radiation will therefore shift over time; however, the Montreal Protocol will continue to have far-reaching benefits for human well-being and environmental sustainability.
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| 13. |
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| 14. |
- Dijkhorst, Phillip J., et al.
(författare)
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Core Set of Patient-Reported Outcome Measures for Measuring Quality of Life in Clinical Obesity Care
- 2024
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Ingår i: Obesity Surgery. - : Springer. - 0960-8923 .- 1708-0428. ; 34:8, s. 2980-2990
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The focus of measuring success in obesity treatment is shifting from weight loss to patients' health and quality of life. The objective of this study was to select a core set of patient-reported outcomes and patient-reported outcome measures to be used in clinical obesity care.Materials and Methods: The Standardizing Quality of Life in Obesity Treatment III, face-to-face hybrid consensus meeting, including people living with obesity as well as healthcare providers, was held in Maastricht, the Netherlands, in 2022. It was preceded by two prior multinational consensus meetings and a systematic review.Results: The meeting was attended by 27 participants, representing twelve countries from five continents. The participants included healthcare providers, such as surgeons, endocrinologists, dietitians, psychologists, researchers, and people living with obesity, most of whom were involved in patient representative networks. Three patient-reported outcome measures (patient-reported outcomes) were selected: the Impact of Weight on Quality of Life-Lite (self-esteem) measure, the BODY-Q (physical function, physical symptoms, psychological function, social function, eating behavior, and body image), and the Quality of Life for Obesity Surgery questionnaire (excess skin). No patient-reported outcome measure was selected for stigma.Conclusion: A core set of patient-reported outcomes and patient-reported outcome measures for measuring quality of life in clinical obesity care is established incorporating patients' and experts' opinions. This set should be used as a minimum for measuring quality of life in routine clinical practice. It is essential that individual patient-reported outcome measure scores are shared with people living with obesity in order to enhance patient engagement and shared decision-making.
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| 15. |
- Johannesson, M, et al.
(författare)
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A resource for the simultaneous high-resolution mapping of multiple quantitative trait loci in rats: the NIH heterogeneous stock
- 2009
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Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1088-9051. ; 19:1, s. 150-158
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Tidskriftsartikel (refereegranskat)abstract
- The laboratory rat (Rattus norvegicus) is a key tool for the study of medicine and pharmacology for human health. A large database of phenotypes for integrated fields such as cardiovascular, neuroscience, and exercise physiology exists in the literature. However, the molecular characterization of the genetic loci that give rise to variation in these traits has proven to be difficult. Here we show how one obstacle to progress, the fine-mapping of quantitative trait loci (QTL), can be overcome by using an outbred population of rats. By use of a genetically heterogeneous stock of rats, we map a locus contributing to variation in a fear-related measure (two-way active avoidance in the shuttle box) to a region on chromosome 5 containing nine genes. By establishing a protocol measuring multiple phenotypes including immunology, neuroinflammation, and hematology, as well as cardiovascular, metabolic, and behavioral traits, we establish the rat HS as a new resource for the fine-mapping of QTLs contributing to variation in complex traits of biomedical relevance.
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| 16. |
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| 17. |
- Montanier, Cedric, et al.
(författare)
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The Active Site of a Carbohydrate Esterase Displays Divergent Catalytic and Noncatalytic Binding Functions
- 2009
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Ingår i: PLoS Biology. - : Public Library of Science (PLoS). - 1545-7885. ; 7:3, s. 687-697
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Tidskriftsartikel (refereegranskat)abstract
- Multifunctional proteins, which play a critical role in many biological processes, have typically evolved through the recruitment of different domains that have the required functional diversity. Thus the different activities displayed by these proteins are mediated by spatially distinct domains, consistent with the specific chemical requirements of each activity. Indeed, current evolutionary theory argues that the colocalization of diverse activities within an enzyme is likely to be a rare event, because it would compromise the existing activity of the protein. In contrast to this view, a potential example of multifunctional recruitment into a single protein domain is provided by CtCel5C-CE2, which contains an N-terminal module that displays cellulase activity and a C-terminal module, CtCE2, which exhibits a noncatalytic cellulose-binding function but also shares sequence identity with the CE2 family of esterases. Here we show that, unlike other CE2 members, the CtCE2 domain displays divergent catalytic esterase and noncatalytic carbohydrate binding functions. Intriguingly, these diverse activities are housed within the same site on the protein. Thus, a critical component of the active site of CtCE2, the catalytic Ser-His dyad, in harness with inserted aromatic residues, confers noncatalytic binding to cellulose whilst the active site of the domain retains its esterase activity. CtCE2 catalyses deacetylation of noncellulosic plant structural polysaccharides to deprotect these substrates for attack by other enzymes. Yet it also acts as a cellulose-binding domain, which promotes the activity of the appended cellulase on recalcitrant substrates. The CE2 family encapsulates the requirement for multiple activities by biocatalysts that attack challenging macromolecular substrates, including the grafting of a second, powerful and discrete noncatalytic binding functionality into the active site of an enzyme. This article provides a rare example of "gene sharing,'' where the introduction of a second functionality into the active site of an enzyme does not compromise the original activity of the biocatalyst.
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| 18. |
- Montanier, Cedric Y., et al.
(författare)
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A novel, noncatalytic carbohydrate-binding module displays specificity for galactose-containing polysaccharides through calcium-mediated oligomerization
- 2011
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Ingår i: Journal of Biological Chemistry. - : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 286:25
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Tidskriftsartikel (refereegranskat)abstract
- The enzymic degradation of plant cell walls plays a central role in the carbon cycle and is of increasing environmental and industrial significance. The catalytic modules of enzymes that catalyze this process are generally appended to noncatalytic carbohydrate-binding modules (CBMs). CBMs potentiate the rate of catalysis by bringing their cognate enzymes into intimate contact with the target substrate. A powerful plant cell wall-degrading system is the Clostridium thermocellum multienzyme complex, termed the "cellulosome." Here, we identify a novel CBM (CtCBM62) within the large C. thermocellum cellulosomal protein Cthe_2193 (defined as CtXyl5A), which establishes a new CBM family. Phylogenetic analysis of CBM62 members indicates that a circular permutation occurred within the family. CtCBM62 binds to D-galactose and L-arabinopyranose in either anomeric configuration. The crystal structures of CtCBM62, in complex with oligosaccharides containing alpha- and beta-galactose residues, show that the ligand-binding site in the beta-sandwich protein is located in the loops that connect the two beta-sheets. Specificity is conferred through numerous interactions with the axial O4 of the target sugars, a feature that distinguishes galactose and arabinose from the other major sugars located in plant cell walls. CtCBM62 displays tighter affinity for multivalent ligands compared with molecules containing single galactose residues, which is associated with precipitation of these complex carbohydrates. These avidity effects, which confer the targeting of polysaccharides, are mediated by calcium-dependent oligomerization of the CBM.
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| 19. |
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| 20. |
- Andrady, Anthony, et al.
(författare)
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Environmental effects of ozone depletion and its interactions with climate change: Progress report, 2016
- 2017
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Ingår i: Photochemical and Photobiological Sciences. - : Springer Science and Business Media LLC. - 1474-9092 .- 1474-905X. ; 16:2, s. 107-145
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Tidskriftsartikel (refereegranskat)abstract
- The Parties to the Montreal Protocol are informed by three Panels of experts. One of these is the Environmental Effects Assessment Panel (EEAP), which deals with two focal issues. The first focus is the effects of UV radiation on human health, animals, plants, biogeochemistry, air quality, and materials. The second focus is on interactions between UV radiation and global climate change and how these may affect humans and the environment. When considering the effects of climate change, it has become clear that processes resulting in changes in stratospheric ozone are more complex than previously believed. As a result of this, human health and environmental issues will be longer-lasting and more regionally variable. Like the other Panels, the EEAPproduces a detailed report every four years; the most recent was published as a series of seven papers in 2015 (Photochem. Photobiol. Sci., 2015, 14, 1–184). In the years in between, the EEAP produces less detailed and shorter Progress Reports of the relevant scientific findings. The most recent of these was for 2015 (Photochem. Photobiol. Sci., 2016, 15, 141–147). The present Progress Report for 2016 assesses some of the highlights and new insights with regard to the interactive nature of the direct and indirect effects of UV radiation, atmospheric processes, and climate change. The more detailed Quadrennial Assessment will bemade available in 2018.
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| 21. |
- Bundred, Nigel J, et al.
(författare)
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Cyclooxygenase-2 inhibition does not improve the reduction in ductal carcinoma in situ proliferation with aromatase inhibitor therapy: results of the ERISAC randomized placebo-controlled trial.
- 2010
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Ingår i: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1078-0432. ; 16:5, s. 1605-12
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Tidskriftsartikel (refereegranskat)abstract
- Tamoxifen reduces risk of recurrence after breast conservation surgery for ductal carcinoma in situ (DCIS), but no data exists on the effectiveness of aromatase inhibitors for DCIS. Cyclooxygenase-2 (COX-2) is overexpressed in DCIS, representing another potential therapeutic target. The aim of the study was to determine the effect of aromatase and/or COX-2 inhibition on epithelial proliferation and apoptosis in a presurgical study of estrogen receptor (ER)-positive DCIS. Methods: Postmenopausal women with ER-positive DCIS diagnosed by core biopsy were randomized to a 2 x 2 design of either 14 days of exemestane or placebo and celecoxib, or placebo immediately before surgery. Paired baseline and end point biopsies were analyzed for proliferation (Ki67), apoptosis, human epidermal growth factor receptor 2 (HER2), COX-2, and progesterone receptor (PR) expression by immunohistochemistry. The primary end point was a decrease in Ki67 between diagnosis and surgical excision.
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| 22. |
- Kitahara, Cari M., et al.
(författare)
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Association between Class III Obesity (BMI of 40-59 kg/m(2)) and Mortality : A Pooled Analysis of 20 Prospective Studies
- 2014
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Ingår i: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prevalence of class III obesity (body mass index [BMI]>= 40 kg/m(2)) has increased dramatically in several countries and currently affects 6% of adults in the US, with uncertain impact on the risks of illness and death. Using data from a large pooled study, we evaluated the risk of death, overall and due to a wide range of causes, and years of life expectancy lost associated with class III obesity. Methods and Findings: In a pooled analysis of 20 prospective studies from the United States, Sweden, and Australia, we estimated sex-and age-adjusted total and cause-specific mortality rates (deaths per 100,000 persons per year) and multivariable-adjusted hazard ratios for adults, aged 19-83 y at baseline, classified as obese class III (BMI 40.0-59.9 kg/m(2)) compared with those classified as normal weight (BMI 18.5-24.9 kg/m(2)). Participants reporting ever smoking cigarettes or a history of chronic disease (heart disease, cancer, stroke, or emphysema) on baseline questionnaires were excluded. Among 9,564 class III obesity participants, mortality rates were 856.0 in men and 663.0 in women during the study period (19762009). Among 304,011 normal-weight participants, rates were 346.7 and 280.5 in men and women, respectively. Deaths from heart disease contributed largely to the excess rates in the class III obesity group (rate differences = 238.9 and 132.8 in men and women, respectively), followed by deaths from cancer (rate differences = 36.7 and 62.3 in men and women, respectively) and diabetes (rate differences = 51.2 and 29.2 in men and women, respectively). Within the class III obesity range, multivariable-adjusted hazard ratios for total deaths and deaths due to heart disease, cancer, diabetes, nephritis/nephrotic syndrome/nephrosis, chronic lower respiratory disease, and influenza/pneumonia increased with increasing BMI. Compared with normal-weight BMI, a BMI of 40-44.9, 45-49.9, 50-54.9, and 55-59.9 kg/m(2) was associated with an estimated 6.5 (95% CI: 5.7-7.3), 8.9 (95% CI: 7.4-10.4), 9.8 (95% CI: 7.4-12.2), and 13.7 (95% CI: 10.5-16.9) y of life lost. A limitation was that BMI was mainly ascertained by self-report. Conclusions: Class III obesity is associated with substantially elevated rates of total mortality, with most of the excess deaths due to heart disease, cancer, and diabetes, and major reductions in life expectancy compared with normal weight.
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| 23. |
- Price, Thomas S, et al.
(författare)
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SW-ARRAY : a dynamic programming solution for the identification of copy-number changes in genomic DNA using array comparative genome hybridization data.
- 2005
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 33:11
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Tidskriftsartikel (refereegranskat)abstract
- Comparative genome hybridization (CGH) to DNA microarrays (array CGH) is a technique capable of detecting deletions and duplications in genomes at high resolution. However, array CGH studies of the human genome noting false negative and false positive results using large insert clones as probes have raised important concerns regarding the suitability of this approach for clinical diagnostic applications. Here, we adapt the Smith-Waterman dynamic-programming algorithm to provide a sensitive and robust analytic approach (SW-ARRAY) for detecting copy-number changes in array CGH data. In a blind series of hybridizations to arrays consisting of the entire tiling path for the terminal 2 Mb of human chromosome 16p, the method identified all monosomies between 267 and 1567 kb with a high degree of statistical significance and accurately located the boundaries of deletions in the range 267-1052 kb. The approach is unique in offering both a nonparametric segmentation procedure and a nonparametric test of significance. It is scalable and well-suited to high resolution whole genome array CGH studies that use array probes derived from large insert clones as well as PCR products and oligonucleotides.
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| 24. |
- Simrén, Magnus, 1966, et al.
(författare)
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Intestinal microbiota in functional bowel disorders: a Rome foundation report.
- 2013
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 62:1, s. 159-76
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Forskningsöversikt (refereegranskat)abstract
- It is increasingly perceived that gut host-microbial interactions are important elements in the pathogenesis of functional gastrointestinal disorders (FGID). The most convincing evidence to date is the finding that functional dyspepsia and irritable bowel syndrome (IBS) may develop in predisposed individuals following a bout of infectious gastroenteritis. There has been a great deal of interest in the potential clinical and therapeutic implications of small intestinal bacterial overgrowth in IBS. However, this theory has generated much debate because the evidence is largely based on breath tests which have not been validated. The introduction of culture-independent molecular techniques provides a major advancement in our understanding of the microbial community in FGID. Results from 16S rRNA-based microbiota profiling approaches demonstrate both quantitative and qualitative changes of mucosal and faecal gut microbiota, particularly in IBS. Investigators are also starting to measure host-microbial interactions in IBS. The current working hypothesis is that abnormal microbiota activate mucosal innate immune responses which increase epithelial permeability, activate nociceptive sensory pathways and dysregulate the enteric nervous system. While we await important insights in this field, the microbiota is already a therapeutic target. Existing controlled trials of dietary manipulation, prebiotics, probiotics, synbiotics and non-absorbable antibiotics are promising, although most are limited by suboptimal design and small sample size. In this article, the authors provide a critical review of current hypotheses regarding the pathogenetic involvement of microbiota in FGID and evaluate the results of microbiota-directed interventions. The authors also provide clinical guidance on modulation of gut microbiota in IBS.
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| 25. |
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| 26. |
- Vardakou, Maria, et al.
(författare)
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Understanding the structural basis for substrate and inhibitor recognition in Eukaryotic GH11 Xylanases
- 2008
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 375:5, s. 1293-1305
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Tidskriftsartikel (refereegranskat)abstract
- Endo-β1,4-xylanases (xylanases) hydrolyse the β1,4 glycosidic bonds in the backbone of xylan. Although xylanases from glycoside hydrolase family 11 (GH11) have been extensively studied, several issues remain unresolved. Thus, the mechanism by which these enzymes hydrolyse decorated xylans is unclear and the structural basis for the variation in catalytic activity within this family is unknown. Furthermore, the mechanism for the differences in the inhibition of fungal GH11 enzymes by the wheat protein XIP-I remains opaque. To address these issues we report the crystal structure and biochemical properties of the Neocallimastix patriciarum xylanase NpXyn11A, which displays unusually high catalytic activity and is one of the few fungal GH11 proteins not inhibited by XIP-I. Although the structure of NpXyn11A could not be determined in complex with substrates, we have been able to investigate how GH11 enzymes hydrolyse decorated substrates by solving the crystal structure of a second GH11 xylanase, EnXyn11A (encoded by an environmental DNA sample), bound to ferulic acid-1,5-arabinofuranose-α1,3-xylotriose (FAX3). The crystal structure of the EnXyn11A–FAX3 complex shows that solvent exposure of the backbone xylose O2 and O3 groups at subsites −3 and +2 allow accommodation of α1,2-linked 4-methyl-D-glucuronic acid and L-arabinofuranose side chains. Furthermore, the ferulated arabinofuranose side chain makes hydrogen bonds and hydrophobic interactions at the +2 subsite, indicating that the decoration may represent a specificity determinant at this aglycone subsite. The structure of NpXyn11A reveals potential −3 and +3 subsites that are kinetically significant. The extended substrate-binding cleft of NpXyn11A, compared to other GH11 xylanases, may explain why the Neocallimastix enzyme displays unusually high catalytic activity. Finally, the crystal structure of NpXyn11A shows that the resistance of the enzyme to XIP-I is not due solely to insertions in the loop connecting β strands 11 and 12, as suggested previously, but is highly complex.
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| 27. |
- Williams, Edward H, et al.
(författare)
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CamGFR v2: A New Model for Estimating the Glomerular Filtration Rate from Standardized or Non-standardized Creatinine in Patients with Cancer.
- 2021
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Ingår i: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1557-3265. ; 27:5, s. 1381-1390
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Tidskriftsartikel (refereegranskat)abstract
- Management of patients with cancer, specifically carboplatin dosing, requires accurate knowledge of glomerular filtration rate (GFR). Direct measurement of GFR is resource limited. Available models for estimated GFR (eGFR) are optimized for patients without cancer and either isotope dilution mass spectrometry (IDMS)- or non-IDMS-standardized creatinine measurements. We present an eGFR model for patients with cancer compatible with both creatinine measurement methods.GFR measurements, biometrics, and IDMS- or non-IDMS-standardized creatinine values were collected for adult patients from three cancer centers. Using statistical modeling, an IDMS and non-IDMS creatinine-compatible eGFR model (CamGFR v2) was developed. Its performance was compared with that of the existing models Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Modification of Diet in Renal Disease (MDRD), Full Age Spectrum (FAS), Lund-Malmö revised, and CamGFR v1, using statistics for bias, precision, accuracy, and clinical robustness.A total of 3,083 IDMS- and 4,612 non-IDMS-standardized creatinine measurements were obtained from 7,240 patients. IDMS-standardized creatinine values were lower than non-IDMS-standardized values in within-center comparisons (13.8% lower in Cambridge; P < 0.0001 and 19.3% lower in Manchester; P < 0.0001), and more consistent between centers. CamGFR v2 was the most accurate [root-mean-squared error for IDMS, 14.97 mL/minute (95% confidence interval, 13.84-16.13) and non-IDMS, 15.74 mL/minute (14.86-16.63)], most clinically robust [proportion with >20% error of calculated carboplatin dose for IDMS, 0.12 (0.09-0.14) and non-IDMS, 0.17 (0.15-0.2)], and least biased [median residual for IDMS, 0.73 mL/minute (-0.68 to 2.2) and non-IDMS, -0.43 mL/minute (-1.48 to 0.91)] eGFR model, particularly when eGFR was larger than 60 ml/minute.CamGFR v2 can utilize IDMS- and non-IDMS-standardized creatinine measurements and outperforms previous models. CamGFR v2 should be examined prospectively as a practice-changing standard of care for eGFR-based carboplatin dosing.
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| 28. |
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| 29. |
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| 30. |
- Baud, A, et al.
(författare)
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Genomes and phenomes of a population of outbred rats and its progenitors
- 2014
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Ingår i: Scientific data. - : Springer Science and Business Media LLC. - 2052-4463. ; 1, s. 140011-
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Tidskriftsartikel (refereegranskat)abstract
- Finding genetic variants that contribute to phenotypic variation is one of the main challenges of modern genetics. We used an outbred population of rats (Heterogeneous Stock, HS) in a combined sequence-based and genetic mapping analysis to identify sequence variants and genes contributing to complex traits of biomedical relevance. Here we describe the sequences of the eight inbred progenitors of the HS and the variants that segregate between them. We report the genotyping of 1,407 HS rats, and the collection from 2,006 rats of 195 phenotypic measures that are relevant to models of anxiety, type 2 diabetes, hypertension and osteoporosis. We make available haplotype dosages for the 1,407 genotyped rats, since genetic mapping in the HS is best carried out by reconstructing each HS chromosome as a mosaic of the progenitor genomes. Finally, we have deposited an R object that makes it easy to incorporate our sequence data into any genetic study of HS rats. Our genetic data are available for both Rnor3.4 and Rnor5.0 rat assemblies.
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| 31. |
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| 32. |
- Constantinidis, Ioannis, et al.
(författare)
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Non-invasive evaluation of alginate/poly-L-lysine/alginate microcapsules by magnetic resonance microscopy
- 2007
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 28:15, s. 2438-2445
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Tidskriftsartikel (refereegranskat)abstract
- In this report, we present data to demonstrate the utility of H-1 MR microscopy to non-invasively examine alginate/poly-L-lysine/ alginate (APA) microcapsules. Specifically, high-resolution images were used to visualize and quantify the poly-L-lysine (PLL) layer, and monitor temporal changes in the alginate gel microstructure during a month long in vitro culture. The thickness of the alginate/PLL layer was quantified to be 40.6 +/- 6.2 mu m regardless of the alginate composition used to generate the beads or the time of alginate/PLL interaction (2, 6, or 20 min). However, there was a notable difference in the contrast of the PLL layer that depended upon the guluronic content of the alginate and the alginate/PLL interaction time. The T-2 relaxation time and the apparent diffusion coefficient (ADC) of the alginate matrix were measured periodically throughout the month long culture period. Alginate beads generated with a high guluronic content alginate demonstrated a temporal decrease in T-2 over the duration of the experiment, while ADC was unaffected. This decrease in T-2 is attributed to a reorganization of the alginate microstructure due to periodic media exchanges that mimicked a regular feeding regiment for cultured cells. In beads coated with a PLL layer, this temporal decrease in T-2 was less pronounced suggesting that the PLL layer helped maintain the integrity of the initial alginate microstructure. Conversely, alginate beads generated with a high mannuronic content alginate (with or without a PLL layer) did not display temporal changes in either T-2 or ADC. This observation suggests that the microstructure of high mannuronic content alginate beads is less susceptible to culture conditions.
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| 33. |
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| 34. |
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| 35. |
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| 36. |
- Flint, Daniel J., et al.
(författare)
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Supply Chain Innovation
- 2007
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Ingår i: Handbook of Global Supply Chain Management. - 1412918057
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 37. |
- Graf, Daniela, et al.
(författare)
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Contribution of diet to the composition of the human gut microbiota.
- 2015
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Ingår i: Microbial Ecology in Health and Disease. - : Co-Action Publishing. - 0891-060X .- 1651-2235. ; 26
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Tidskriftsartikel (refereegranskat)abstract
- In the human gut, millions of bacteria contribute to the microbiota, whose composition is specific for every individual. Although we are just at the very beginning of understanding the microbiota concept, we already know that the composition of the microbiota has a profound impact on human health. A key factor in determining gut microbiota composition is diet. Preliminary evidence suggests that dietary patterns are associated with distinct combinations of bacteria in the intestine, also called enterotypes. Western diets result in significantly different microbiota compositions than traditional diets. It is currently unknown which food constituents specifically promote growth and functionality of beneficial bacteria in the intestine. The aim of this review is to summarize the recently published evidence from human in vivo studies on the gut microbiota-modulating effects of diet. It includes sections on dietary patterns (e.g. Western diet), whole foods, food constituents, as wells as food-associated microbes and their influence on the composition of human gut microbiota. The conclusions highlight the problems faced by scientists in this fast-developing field of research, and the need for high-quality, large-scale human dietary intervention studies.
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| 38. |
- Jayawickrama, Ravisha S., et al.
(författare)
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Assessing explicit weight bias among Australian health care students : Suitability of the Beliefs About Obese Persons Scale (BAOP) and the Antifat Attitudes Questionnaire (AFA).
- 2023
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Ingår i: Stigma and Health. - : American Psychological Association (APA). - 2376-6972 .- 2376-6964.
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to examine the suitability of the Beliefs About Obese Persons Scale (BAOP) and Antifat Attitudes Questionnaire (AFA) among Australian health care students. Specifically, we explored the factor structures of the two scales, their psychometric properties including internal consistency and convergent validity, and whether they were impacted by social desirability bias. Students studying health care courses at Australian universities (N = 900) responded to an online survey and completed the BAOP, AFA, 13-item Short Form Marlowe–Crowne Social Desirability Scale (MCSDS), Empathy for Obese Patients, and Confidence in Clinical Interaction With Obese Patients scales. Confirmatory factor analyses, Pearson’s correlations, and linear regressions were conducted to examine the factor structures of the BAOP and AFA, examine their convergent validity, and whether scores on these scales were associated with socially desirable responding. Confirmatory factor analyses confirmed the originally proposed factor structures of the BAOP (one factor) and AFA (three factors) and supported a relatively good model fit. Support for convergent validity of the two measures was shown when correlated with each other and the Empathy for Obese Patients and Confidence in Clinical Interaction With Obese Patients scales. The BAOP was not associated with socially desirable responding (p > .5). In contrast, all subscales of the AFA were associated with socially desirable responding (p < .5); as AFA scores increased, participants were less likely to respond in a socially desirable manner. The BAOP and AFA are considerably suitable measures to assess explicit weight bias among Australian health care students.Our findings indicate that the Beliefs About Obese Persons Scale (BAOP) and Antifat Attitudes Questionnaire (AFA) are considerably suitable measures to assess explicit weight bias among Australian health care students. Our findings support the continued assessment of explicit weight bias among health care students in order to quantify this construct within this population. Quantifying the extent to which explicit weight bias is present among health care students may assist in the development of novel weight bias reduction interventions to reduce students’ exhibited weight bias, with the goal of enabling future health care professionals to provide equitable treatment to people living with overweight.
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| 39. |
- Jayawickrama, Ravisha S, et al.
(författare)
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Explicit and implicit weight bias among health care students : a cross-sectional study of 39 Australian universities.
- 2023
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Ingår i: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 58
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Weight bias exhibited by health care students may continue into their future practice, compromising the provision of care that people living with overweight or obesity receive. This highlights the need to comprehensively examine the extent to which weight bias is present among health care students and the factors that may be associated with students' weight bias.METHODS: In this cross-sectional study, Australian university students enrolled in health care courses were invited via social media advertisements, snowball and convenience sampling, and by making direct contact with universities to complete an online survey. Students provided demographic information including discipline of study, perceived weight status, and state of residence. Students then completed several measures which assessed their explicit and implicit weight bias, and empathy. Descriptive statistics established the presence of explicit and implicit weight bias, and ANCOVAs, ANOVA, and multiple regression analyses were conducted to examine the potential factors associated with students' exhibited weight bias.FINDINGS: Between March 08, 2022, and March 15, 2022, 900 eligible health care students attending 39 Australian universities participated in the study. Students reported varying levels of explicit and implicit weight bias, with minimal differences between disciplines on most outcome measures. Students who identified as men (vs. women) exhibited higher of both explicit and implicit bias (Beliefs About Obese Persons (BAOP): p = 0.0002, Antifat Attitudes Questionnaire (AFA)-Dislike: p = 0.019, AFA Willpower p < 0.0001, Empathy for Obese Patients: p = 0.0011, Implicit Association Test: p = 0.022), and students who displayed greater (vs. less) empathic concern exhibited lower levels of explicit bias (BAOP, AFA Dislike and Willpower, and Empathy for Obese Patients: p < 0.0001). Having witnessed the enactment of weight stigma sporadically (vs. regularly) by role models was associated with greater attribution of the causes of obesity to willpower (a few times a month vs. daily: p = 0.020, a few times a year vs. daily: p = 0.022), and less time spent with people living with overweight or obesity outside of study was associated with more dislike (a few times a month vs. daily: p = 0.0048, once a month vs. daily: p = 0.0002) and less fear of fat (once a month vs. daily: p = 0.036, and once a month vs. a few times a week: p = 0.0028).INTERPRETATION: Results demonstrate the presence of both explicit and implicit weight bias among Australian health care students. Several characteristics and experiences of students were associated with their weight bias. Validity of the exhibited weight bias should be established in practical interactions with people living with overweight or obesity and novel interventions should be developed to ameliorate weight bias.FUNDING: Research Training Program (RTP) Scholarship, Australian Government, Department of Education.
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| 40. |
- Krog-Mikkelsen, Inger, et al.
(författare)
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A Low Glycemic Index Diet Does Not Affect Postprandial Energy Metabolism but Decreases Postprandial Insulinemia and Increases Fullness Ratings in Healthy Women
- 2011
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Ingår i: Journal of Nutrition. - : Elsevier BV. - 1541-6100 .- 0022-3166. ; 141:9, s. 1679-1684
-
Tidskriftsartikel (refereegranskat)abstract
- At present, it is difficult to determine whether glycemic index (GI) is an important tool in the prevention of lifestyle diseases, and long-term studies investigating GI with diets matched in macronutrient composition, fiber content, energy content, and energy density are still scarce. We investigated the effects of 2 high-carbohydrate (55%) diets with low GI (LGI; 79) or high GI (HGI; 103) on postprandial blood profile, subjective appetite sensations, energy expenditure (EE), substrate oxidation rates, and ad libitum energy intake (El) from a corresponding test meal (LGI or HGI) after consuming the diets ad libitum for 10 wk. Two groups of a total of 29 healthy, overweight women (age: 30.5 +/- 6.6 y; BMI: 27.6 +/- 1.5 kg/m(2)) participated in the 10-wk intervention and a subsequent 4-h meal test. The breakfast test meals differed in GI but were equal in total energy, macronutrient composition, fiber content, and energy density. The LGI meal resulted in lower plasma glucose, serum insulin, and plasma glucagon-like peptide (GLP)-1 and higher plasma glucose-dependent insulinotropic polypeptide concentrations than the HGI meal (P <= 0.05). Ratings of fullness were slightly higher and the desire to eat something fatty was lower after the test meal in the LGI group (P < 0.05). Postprandial plasma GLP-2, plasma glucagon, serum leptin, plasma ghrelin, EE, substrate oxidation rates, and ad libitum El at lunch did not differ between groups. In conclusion, postprandial glycemia, insulinemia, and subjective appetite ratings after a test meal were better after 10-wk ad libitum intake of a LGI compared to a HGI diet. EE and substrate oxidation rates were, however, not affected. These findings give some support to recommendations to consume a LGI diet. J. Nutr. 141: 1679-1684, 2011.
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| 41. |
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| 42. |
- Mills, Nicholas L., et al.
(författare)
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Combustion-derived nanoparticulate induces the adverse vascular effects of diesel exhaust inhalation
- 2011
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Ingår i: European Heart Journal. - London : Academic Press. - 0195-668X .- 1522-9645. ; 32:21, s. 2660-2671
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: Exposure to road traffic and air pollution may be a trigger of acute myocardial infarction, but the individual pollutants responsible for this effect have not been established. We assess the role of combustion-derived-nanoparticles in mediating the adverse cardiovascular effects of air pollution. Methods and results: To determine the in vivo effects of inhalation of diesel exhaust components, 16 healthy volunteers were exposed to (i) dilute diesel exhaust, (ii) pure carbon nanoparticulate, (iii) filtered diesel exhaust, or (iv) filtered air, in a randomized double blind cross-over study. Following each exposure, forearm blood flow was measured during intra-brachial bradykinin, acetylcholine, sodium nitroprusside, and verapamil infusions. Compared with filtered air, inhalation of diesel exhaust increased systolic blood pressure (145 +/- 4 vs. 133 +/- 3 mmHg, P < 0.05) and attenuated vasodilatation to bradykinin (P = 0.005), acetylcholine (P = 0.008), and sodium nitroprusside (P < 0.001). Exposure to pure carbon nanoparticulate or filtered exhaust had no effect on endothelium-dependent or -independent vasodilatation. To determine the direct vascular effects of nanoparticulate, isolated rat aortic rings (n = 6-9 per group) were assessed in vitro by wire myography and exposed to diesel exhaust particulate, pure carbon nanoparticulate and vehicle. Compared with vehicle, diesel exhaust particulate (but not pure carbon nanoparticulate) attenuated both acetylcholine (P < 0.001) and sodium-nitroprusside (P = 0.019)-induced vasorelaxation. These effects were partially attributable to both soluble and insoluble components of the particulate. Conclusion: Combustion-derived nanoparticulate appears to predominately mediate the adverse vascular effects of diesel exhaust inhalation. This provides a rationale for testing environmental health interventions targeted at reducing traffic-derived particulate emissions.
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| 43. |
- Offer, Samuel, et al.
(författare)
-
The association between childhood trauma and overweight and obesity in young adults : the mediating role of food addiction.
- 2022
-
Ingår i: Eating and Weight Disorders. - : Springer. - 1124-4909 .- 1590-1262. ; 27:8, s. 3257-3266
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Childhood trauma is associated with increased risk of obesity during adulthood, which may be associated with the development of food addiction. This study examined whether food addiction mediated the relationship between childhood trauma and obesity in young adults.METHODS: A sample of 512 young adults, aged 18 to 30 years, living with overweight and obesity (Body Mass Index ≥ 25 kg/m2), from the United Kingdom participated in the study. Participants completed the Childhood Trauma Questionnaire (CTQ), the Yale Food Addiction Scale, and provided their current height and weight to compute their Body Mass Index (BMI).RESULTS: Using the PROCESS macro, a mediation analysis found that food addiction accounted for 45% of variance in the relationship between childhood trauma and BMI. Post hoc analyses were conducted to examine the mediating effect of food addiction across each of the five subscales of the CTQ (emotional/physical/sexual abuse and emotional/physical neglect). Food addiction accounted for 32% to 51% of the variance in the relationship between each CTQ subscale and BMI.CONCLUSIONS: These findings suggest that experiences of childhood trauma are associated with the development of overweight and obesity during early adulthood and up to half of this relationship can be attributed to food addiction, which is likely used as a maladaptive coping mechanism in response to trauma. Young adults living with overweight and obesity who report experiences of childhood trauma may benefit from the support of clinical and counselling psychologists to improve their understanding of the underlying psychosocial factors that influence their eating behaviours.LEVEL OF EVIDENCE: Level V, cross-sectional analytic study.
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| 44. |
- O'Keefe, Brian J., et al.
(författare)
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Designing Blended Experiences : Laugh Traders
- 2023
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Ingår i: C&C '23. - New York, NY : Association for Computing Machinery (ACM). - 9798400701801 - 9781450383769 ; , s. 116-128
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Konferensbidrag (refereegranskat)abstract
- Digital transformation is increasingly blurring the line between what is software and what is the world, requiring designers to harmoniously blend digital and physical products, services and spaces if they want to orchestrate meaningful experiences that are specifically aimed at the interweaving relationships between people, places and things. Traditional approaches to product design, interaction design, and user experience design do not often take this new context into account. The pictorial details the results of a twelve-day workshop focusing on real-world audience and performer problems during the Edinburgh Festival Fringe: it illustrates how two distinct tools, the Blended Experiences Tool and the Evaluation Tool, focusing on the creation of a blended experience and respectively meant to provide a structured way to approach the generative and reflective stages of the design process, can be used to address this gap. This pictorial illustrates the theoretical framing supporting the Blended Experiences Tool; describes how the workshop produced Laugh Traders, a speculative experience centering on attending and reviewing comedy shows; provides a page-by-page pictorial storyboard of the Laugh Trader experience; introduces the Evaluation Tool and applies it to Laugh Trader to measure the relevance, complexity, and attractiveness of the resulting blended experience. Preliminary reflections conclude the pictorial. © 2023 ACM.
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| 45. |
- Okeefe, Brian J., et al.
(författare)
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Designing Blended Experiences Workshop : Pedagogies across digital and physical spaces
- 2024
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Ingår i: DIS 2024. - New York, NY : Association for Computing Machinery (ACM). - 9798400706325 ; , s. 429-432
-
Konferensbidrag (refereegranskat)abstract
- Digital transformation is increasingly blurring the line between what software is and what the physical world can be. This requires designers to harmoniously blend digital and physical products, services, and spaces to orchestrate meaningful experiences specifically aimed at the interweaving relationships between people, places, and things. As technologies and subsequent experiences rapidly become increasingly ubiquitous, it is essential to design pedagogy for these technologies at a human scale. The Pedagogies of Designing Blended Experiences workshop will discuss, present, ideate, and propose novel methods and techniques to develop pedagogies toward this need. The full-day workshop outcomes mainly revolve around a) Identifying key pedagogical problems and obstacles when designing across digital and physical spaces, b) Early ideation techniques for novel pedagogical approaches, and c) A three-phased speculative road-map to incorporate workshop outcomes in higher education learning. © 2024 ACM.
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| 46. |
- Okeefe, B. J., et al.
(författare)
-
Designing Blended Experiences Workshop : Pedagogies across digital and physical spaces
- 2024
-
Ingår i: DIS '24 Companion: Companion Publication of the 2024 ACM Designing Interactive Systems Conference. - New York, NY : ACM Digital Library. - 9798400706325 ; , s. 429-432
-
Konferensbidrag (refereegranskat)abstract
- Digital transformation is increasingly blurring the line between what software is and what the physical world can be. This requires designers to harmoniously blend digital and physical products, services, and spaces to orchestrate meaningful experiences specifically aimed at the interweaving relationships between people, places, and things. As technologies and subsequent experiences rapidly become increasingly ubiquitous, it is essential to design pedagogy for these technologies at a human scale. The Pedagogies of Designing Blended Experiences workshop will discuss, present, ideate, and propose novel methods and techniques to develop pedagogies toward this need. The full-day workshop outcomes mainly revolve around a) Identifying key pedagogical problems and obstacles when designing across digital and physical spaces, b) Early ideation techniques for novel pedagogical approaches, and c) A three-phased speculative road-map to incorporate workshop outcomes in higher education learning.
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| 47. |
- Petrican, Raluca, et al.
(författare)
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Electroconvulsive therapy "corrects" the neural architecture of visuospatial memory : Implications for typical cognitive-affective functioning
- 2019
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Ingår i: NeuroImage. - : Elsevier BV. - 2213-1582. ; 23
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Tidskriftsartikel (refereegranskat)abstract
- Although electroconvulsive therapy (ECT) is a widely used and effective treatment for refractory depression, the neural underpinnings of its therapeutic effects remain poorly understood. To address this issue, here, we focused on a core cognitive deficit associated with depression, which tends to be reliably ameliorated through ECT, specifically, the ability to learn visuospatial information. Thus, we pursued three goals. First, we tested whether ECT can "normalize" the functional brain organization patterns associated with visuospatial memory and whether such corrections would predict post-ECT improvements in learning visuospatial information. Second, we investigated whether, among healthy individuals, stronger expression of the neural pattern, susceptible to adjustments through ECT, would predict reduced incidence of depression-relevant cognition and affect. Third, we sought to quantify the heritability of the ECT-correctable neural profile. Thus, in a task fMRI study with a clinical and a healthy comparison sample, we characterized two functional connectome patterns: one that typifies trait depression (i.e., differentiates patients from healthy individuals) and another that is susceptible to "normalization" through ECT. Both before and after ECT, greater expression of the trait depression neural profile was associated with more frequent repetitive thinking about past personal events (affective persistence), a hallmark of depressogenic cognition. Complementarily, post-treatment, stronger expression of the ECT-corrected neural profile was linked to improvements in visuospatial learning, a mental ability which is markedly impaired in depression. Subsequently, using data from the Human Connectome Project (HCP) (N = 333), we demonstrated that the functional brain organization of healthy participants with greater levels of subclinical depression and higher incidence of its associated cognitive deficits (affective persistence, impaired learning) shows greater similarity to the trait depression neural profile and reduced similarity to the ECT-correctable neural profile, as identified in the patient sample. These results tended to be specific to learning-relevant task contexts (working memory, perceptual relational processing). Genetic analyses based on HCP twin data (N = 128 pairs) suggested that, among healthy individuals, a functional brain organization similar to the one normalized by ECT in the patient sample is endogenous to cognitive contexts that require visuospatial processing that extends beyond the here-and-now. Broadly, the present findings supported our hypothesis that some of the therapeutic effects of ECT may be due to its correcting the expression of a naturally occurring pattern of functional brain organization that facilitates integration of internal and external cognition beyond the immediate present. Given their substantial susceptibility to both genetic and environmental effects, such mechanisms may be useful both for identifying at risk individuals and for monitoring progress of interventions targeting mood-related pathology.
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| 48. |
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| 49. |
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| 50. |
- Udayappan, Shanthadevi, et al.
(författare)
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Oral treatment with Eubacterium hallii improves insulin sensitivity in db/db mice
- 2016
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Ingår i: npj Biofilms and Microbiomes. - : Springer Science and Business Media LLC. - 2055-5008. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- © The Author(s) 2016. An altered intestinal microbiota composition is associated with insulin resistance and type 2 diabetes mellitus. We previously identified increased intestinal levels of Eubacterium hallii, an anaerobic bacterium belonging to the butyrate-producing Lachnospiraceae family, in metabolic syndrome subjects who received a faecal transplant from a lean donor. To further assess the effects of E. hallii on insulin sensitivity, we orally treated obese and diabetic db/db mice with alive E. hallii and glycerol or heatinactive E. hallii as control. Insulin tolerance tests and hyperinsulinemic-euglycemic clamp experiments revealed that alive E. hallii treatment improved insulin sensitivity compared control treatment. In addition, E. hallii treatment increased energy expenditure in db/db mice. Active E. hallii treatment was found to increase faecal butyrate concentrations and to modify bile acid metabolism compared with heat-inactivated controls. Our data suggest that E. hallii administration potentially alters the function of the intestinal microbiome and that microbial metabolites may contribute to the improved metabolic phenotype.
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