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- Machiela, Mitchell J., et al.
(författare)
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Characterization of Large Structural Genetic Mosaicism in Human Autosomes
- 2015
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 96:3, s. 487-497
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Tidskriftsartikel (refereegranskat)abstract
- Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 3 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
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| 6. |
- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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- Jacobs, Kevin B, et al.
(författare)
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Detectable clonal mosaicism and its relationship to aging and cancer.
- 2012
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Ingår i: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658
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Tidskriftsartikel (refereegranskat)abstract
- In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
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- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 13. |
- Machiela, Mitchell J, et al.
(författare)
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Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome
- 2016
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.
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| 15. |
- Carville, S F, et al.
(författare)
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EULAR evidence-based recommendations for the management of fibromyalgia syndrome
- 2008
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 67:4, s. 536-541
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To develop evidence-based recommendations for the management of fibromyalgia syndrome. Methods: A multidisciplinary task force was formed representing 11 European countries. The design of the study, including search strategy, participants, interventions, outcome measures, data collection and analytical method, was defined at the outset. A systematic review was undertaken with the keywords "fibromyalgia", "treatment or management" and "trial". Studies were excluded if they did not utilise the American College of Rheumatology classification criteria, were not clinical trials, or included patients with chronic fatigue syndrome or myalgic encephalomyelitis. Primary outcome measures were change in pain assessed by visual analogue scale and fibromyalgia impact questionnaire. The quality of the studies was categorised based on randomisation, blinding and allocation concealment. Only the highest quality studies were used to base recommendations on. When there was insufficient evidence from the literature, a Delphi process was used to provide basis for recommendation. Results: 146 studies were eligible for the review. 39 pharmacological intervention studies and 59 non-pharmacological were included in the final recommendation summary tables once those of a lower quality or with insufficient data were separated. The categories of treatment identified were antidepressants, analgesics, and "other pharmacological" and exercise, cognitive behavioural therapy, education, dietary interventions and "other non-pharmacological". In many studies sample size was small and the quality of the study was insufficient for strong recommendations to be made. Conclusions: Nine recommendations for the management of fibromyalgia syndrome were developed using a systematic review and expert consensus.
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| 16. |
- Dahlrot, R. H., et al.
(författare)
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Prognostic value of O-6-methylguanine-DNA methyltransferase (MGMT) protein expression in glioblastoma excluding nontumour cells from the analysis
- 2018
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Ingår i: Neuropathology and Applied Neurobiology. - : Wiley. - 0305-1846 .- 1365-2990. ; 44:2, s. 172-184
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Tidskriftsartikel (refereegranskat)abstract
- Aims: It is important to predict response to treatment with temozolomide (TMZ) in glioblastoma (GBM) patients. Both MGMT protein expression and MGMT promoter methylation status have been reported to predict the response to TMZ. We investigated the prognostic value of quantified MGMT protein levels in tumour cells and the prognostic importance of combining information of MGMT protein level and MGMT promoter methylation status.Methods: MGMT protein expression was quantified in tumour cells in 171 GBMs from the population‐based Region of Southern Denmark (RSD)‐cohort using a double immunofluorescence approach. Pyrosequencing was performed in 157 patients. For validation we used GBM‐patients from a Nordic Study (NS) investigating the effect of radiotherapy and different TMZ schedules.Results: When divided at the median, patients with low expression of MGMT protein (AF‐low) had the best prognosis (HR = 1.5, P = 0.01). Similar results were observed in the subgroup of patients receiving the Stupp regimen (HR = 2.0, P = 0.001). In the NS‐cohort a trend towards superior survival (HR = 1.6, P = 0.08) was seen in patients with AF‐low. Including MGMT promoter methylation status, we found for both cohorts that patients with methylated MGMT promoter and AF‐low had the best outcome; median OS 23.1 and 20.0 months, respectively.Conclusion: Our data indicate that MGMT protein expression in tumour cells has an independent prognostic significance. Exclusion of nontumour cells contributed to a more exact analysis of tumour‐specific MGMT protein expression. This should be incorporated in future studies evaluating MGMT status before potential integration into clinical practice.
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| 17. |
- Henriksson, Pontus, et al.
(författare)
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A Smartphone App to Promote Healthy Weight Gain, Diet, and Physical Activity During Pregnancy (HealthyMoms) : Protocol for a Randomized Controlled Trial
- 2019
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Ingår i: JMIR Research Protocols. - : JMIR Publications Inc.. - 1929-0748. ; 8:3
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Excessive gestational weight gain is common and associated with adverse outcomes both in the short and long term. Although traditional lifestyle-based interventions have shown to mitigate excess gestational weight gain, little is known about whether mobile Health (mHealth) apps can promote healthy weight gain, diet, and physical activity during pregnancy.OBJECTIVE: The primary aim of the HealthyMoms trial is to determine the effectiveness of a smartphone app (HealthyMoms) for mitigating excess gestational weight gain during pregnancy. Secondary aims are to determine the effectiveness of the app on dietary habits, physical activity, body fatness, and glycemia during pregnancy.METHODS: HealthyMoms is a two-arm randomized controlled trial. Women are being recruited at routine visits at the maternity clinics in Linköping, Norrköping and Motala, Sweden. Women are randomized to the control or intervention group (n=150 per group). All women will receive standard care, and women in the intervention group will also receive the HealthyMoms smartphone app.RESULTS: Recruitment of participants to the trial was initiated in October 2017, and 190 women have so far completed the baseline measurement. The baseline measures are estimated to be finalized in December 2019, and the follow-up measures are estimated to be completed in June 2020.CONCLUSIONS: This project will evaluate a novel smartphone app intervention integrated with existing maternity health care. If successful, it has great potential to be implemented nationally in order to promote healthy weight gain and health behaviors during pregnancy.INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/13011.
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- Bach, D, et al.
(författare)
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Expression of Mfn2, the Charcot-Marie-Tooth neuropathy type 2A gene, in human skeletal muscle: effects of type 2 diabetes, obesity, weight loss, and the regulatory role of tumor necrosis factor alpha and interleukin-6
- 2005
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 54:9, s. 2685-2693
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Tidskriftsartikel (refereegranskat)abstract
- The primary gene mutated in Charcot-Marie-Tooth type 2A is mitofusin-2 (Mfn2). Mfn2 encodes a mitochondrial protein that participates in the maintenance of the mitochondrial network and that regulates mitochondrial metabolism and intracellular signaling. The potential for regulation of human Mfn2 gene expression in vivo is largely unknown. Based on the presence of mitochondrial dysfunction in insulin-resistant conditions, we have examined whether Mfn2 expression is dysregulated in skeletal muscle from obese or nonobese type 2 diabetic subjects, whether muscle Mfn2 expression is regulated by body weight loss, and the potential regulatory role of tumor necrosis factor (TNF)α or interleukin-6. We show that mRNA concentration of Mfn2 is decreased in skeletal muscle from both male and female obese subjects. Muscle Mfn2 expression was also reduced in lean or in obese type 2 diabetic patients. There was a strong negative correlation between the Mfn2 expression and the BMI in nondiabetic and type 2 diabetic subjects. A positive correlation between the Mfn2 expression and the insulin sensitivity was also detected in nondiabetic and type 2 diabetic subjects. To determine the effect of weight loss on Mfn2 mRNA expression, six morbidly obese subjects were subjected to weight loss by bilio-pancreatic diversion. Mean expression of muscle Mfn2 mRNA increased threefold after reduction in body weight, and a positive correlation between muscle Mfn2 expression and insulin sensitivity was again detected. In vitro experiments revealed an inhibitory effect of TNFα or interleukin-6 on Mfn2 expression in cultured cells. We conclude that body weight loss upregulates the expression of Mfn2 mRNA in skeletal muscle of obese humans, type 2 diabetes downregulates the expression of Mfn2 mRNA in skeletal muscle, Mfn2 expression in skeletal muscle is directly proportional to insulin sensitivity and is inversely proportional to the BMI, TNFα and interleukin-6 downregulate Mfn2 expression and may participate in the dysregulation of Mfn2 expression in obesity or type 2 diabetes, and the in vivo modulation of Mfn2 mRNA levels is an additional level of regulation for the control of muscle metabolism and could provide a molecular mechanism for alterations in mitochondrial function in obesity or type 2 diabetes.
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| 27. |
- Bendtsen, Marcus, 1982-, et al.
(författare)
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mHealth intervention for multiple lifestyle behaviour change among high school students in Sweden (LIFE4YOUth) : Protocol for a randomised controlled trial
- 2021
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Ingår i: Public Health Nursing. - : BMC. - 0737-1209 .- 1525-1446 .- 1471-2458. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundNational surveys in Sweden demonstrate that the majority of young people do not engage in health promoting behaviours at levels recommended by the Public Health Agency of Sweden. The objective of this study is to estimate the effectiveness of a novel mHealth intervention named LIFE4YOUth, which targets multiple lifestyle behaviours (alcohol, diet, physical activity, and smoking) among high school students in Sweden.MethodsA 2-arm parallel groups single blind randomised controlled trial (1:1) will be employed to estimate the effectiveness of the novel mHealth intervention. Students will be recruited at high schools throughout Sweden, and will be included if they fulfil one of six criteria relating to unhealthy behaviours with respect to alcohol, diet, physical activity and smoking. Eligible participants will be randomised to either receive the novel intervention immediately, or to be placed on a waiting list for 4 months. The intervention consists of a combination of recurring screening, text messages, and an interactive platform which is adaptable to individual preferences. Outcome measures with respect to alcohol, diet, physical activity and smoking will be assessed through questionnaires at 2 and 4 months post randomisation.DiscussionThe findings of this trial could be generalised to a diverse high-school student population as our recruitment encompass a large proportion of schools throughout Sweden with various educational profiles. Furthermore, if effective, the mHealth intervention has good potential to be able to be scaled up and disseminated at high schools nationally.Trial registrationRegistered prospectively on 2020-05-20 in ISRCTN (ISRCTN34468623).
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| 28. |
- Bergström, I., et al.
(författare)
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Compressive loading of the murine tibia reveals site-specific micro-scale differences in adaptation and maturation rates of bone
- 2017
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 28:3, s. 1121-1131
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Tidskriftsartikel (refereegranskat)abstract
- Summary: Loading increases bone mass and strength in a site-specific manner; however, possible effects of loading on bone matrix composition have not been evaluated. Site-specific structural and material properties of mouse bone were analyzed on the macro- and micro/molecular scale in the presence and absence of axial loading. The response of bone to load is heterogeneous, adapting at molecular, micro-, and macro-levels. Introduction: Osteoporosis is a degenerative disease resulting in reduced bone mineral density, structure, and strength. The overall aim was to explore the hypothesis that changes in loading environment result in site-specific adaptations at molecular/micro- and macro-scale in mouse bone. Methods: Right tibiae of adult mice were subjected to well-defined cyclic axial loading for 2 weeks; left tibiae were used as physiologically loaded controls. The bones were analyzed with μCT (structure), reference point indentation (material properties), Raman spectroscopy (chemical), and small-angle X-ray scattering (mineral crystallization and structure). Results: The cranial and caudal sites of tibiae are structurally and biochemically different within control bones. In response to loading, cranial and caudal sites increase in cortical thickness with reduced mineralization (−14 and −3%, p < 0.01, respectively) and crystallinity (−1.4 and −0.3%, p < 0.05, respectively). Along the length of the loaded bones, collagen content becomes more heterogeneous on the caudal site and the mineral/collagen increases distally at both sites. Conclusion: Bone structure and composition are heterogeneous, finely tuned, adaptive, and site-specifically responsive at the micro-scale to maintain optimal function. Manipulation of this heterogeneity may affect bone strength, relative to specific applied loads.
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| 30. |
- Cadenas-Sanchez, Cristina, et al.
(författare)
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Differences in Brain Volume between Metabolically Healthy and Unhealthy Overweight and Obese Children : The Role of Fitness
- 2020
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 9:4
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to examine whether metabolically healthy overweight/obese children have greater global and regional gray matter volumes than their metabolically unhealthy peers. We further examined the association between gray matter volume and academic achievement, along with the role of cardiorespiratory fitness in these associations. A total of 97 overweight/obese children (10.0 +/- 1.2 years) participated. We classified children as metabolically healthy/unhealthy based on metabolic syndrome cut-offs. Global and regional brain volumes were assessed by magnetic resonance imaging. Academic achievement was assessed using the Woodcock-Munoz standardized test. Cardiorespiratory fitness was assessed by the 20 m shuttle run test. Metabolically healthy overweight/obese (MHO) children had greater regional gray matter volume compared to those who were metabolically unhealthy (MUO) (all p <= 0.001). A similar trend was observed for global gray matter volume (p = 0.06). Global gray matter volume was positively related to academic achievement (beta = 0.237, p = 0.036). However, all the associations were attenuated or disappeared after adjusting for cardiorespiratory fitness (p > 0.05). The findings of the present study support that metabolically healthy overweight/obese children have greater gray matter volume compared to those that are metabolically unhealthy, which is in turn related to better academic achievement. However, cardiorespiratory fitness seems to explain, at least partially, these findings.
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| 31. |
- Cadenas-Sanchez, Cristina, et al.
(författare)
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Fitness, physical activity and academic achievement in overweight/obese children
- 2020
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Ingår i: Journal of Sports Sciences. - : TAYLOR & FRANCIS LTD. - 0264-0414 .- 1466-447X. ; 38:7, s. 731-740
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to examine the associations of fitness and physical activity with academic achievement in children with overweight/obesity. A total of 106 (10.0 +/- 1.1y, 61 boys) children participated. The fitness components were assessed by field and laboratory-based tests. Physical activity was measured via accelerometry. The academic achievement was assessed by a standardised test and school-grades. Field-based cardiorespiratory fitness was associated with language skills (ss-standardised- ranging from 0.281 to 0.365, p amp;lt; 0.01). The field-based muscular strength was associated with grade point average, natural and social sciences, and foreign language (ss = 0.280-0.326, all p amp;lt;= 0.01). Speed-agility was associated with some language-related skills (ss = 0.325-0.393, all p amp;lt;= 0.01). The laboratory-based muscular strength also showed an association with mathematics skills (ss = 0.251-0.306, all p amp;lt;= 0.01). Physical activity did not show significant association with academic achievement (p amp;gt; 0.01). Overall, the significant associations observed for muscular strength and speed/agility were attenuated and disappeared in many cases after additional adjustments for body mass index and cardiorespiratory fitness, indicating that these associations are inter-dependent. Our study contributes by indicating that other fitness components apart from cardiorespiratory fitness, such as muscular strength and speed-agility, are positively associated with academic achievement. However, these associations appear to be dependent on body mass index and cardiorespiratory fitness.
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| 35. |
- Degen, Winfried G. J., et al.
(författare)
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Characterization of recombinant human autoantibody fragments directed toward the autoantigenic U1-70K protein
- 2000
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Ingår i: European Journal of Immunology. - : Wiley-VCH Verlagsgesellschaft. - 0014-2980 .- 1521-4141. ; 30:10, s. 3029-3038
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Tidskriftsartikel (refereegranskat)abstract
- The U1-70K protein is specifically bound to stemloop I of the U1 small nuclear RNA contained in the U1 small nuclear ribonucleoprotein complex (U1 snRNP), which is involved in the splicing of pre-mRNA. All components of the U1 snRNP complex, including the U1-70K protein, are important autoantigens in patients with systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). Here we describe for the first time the selection and characterization of recombinant human anti-U1-70K single chain autoantibody fragments (anti-hU1-70K scFv) from autoimmune patient-derived phage display antibody libraries. All scFv specifically recognize parts of the hU1-70K protein and its apoptotic 40-kDa cleavage product. In Western blotting assays a number of scFv preferentially recognize the 40-kDa apoptotic cleavage fragment of the U1-70K protein, suggesting a possible involvement of this apoptotic cleavage product in the autoimmune response of patients. The germline gene usage of these recombinant autoantibodies was also determined. Using several U1-70K deletion and point mutants of both human (h) and Drosophila melanogaster (Dm) origin, it was established that the U1-70K epitope that is recognized by the anti-hU1-70K scFv is located within the RNA binding domain.
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| 37. |
- Efe, C., et al.
(författare)
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Validation of Risk Scoring Systems in Ursodeoxycholic Acid-Treated Patients With Primary Biliary Cholangitis
- 2019
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Ingår i: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270 .- 1572-0241. ; 114:7, s. 1101-1108
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Risk stratification based on biochemical variables is a useful tool for monitoring ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC). Several UDCA response criteria and scoring systems have been proposed for risk prediction in PBC, but these have not been validated in large external cohorts. METHODS: We performed a study on data of 1746 UDCA-treated patients with PBC from 25 centers in Europe, United States, and Canada. The prognostic performance of the risk scoring systems (GLOBE and UK-PBC) and the UDCA response criteria (Barcelona, Paris I, Paris II, Rotterdam, and Toronto) were evaluated. We regarded cirrhosis-related complications (ascites, variceal bleeding, and/or hepatic encephalopathy) as clinical end points. RESULTS: A total of 171 patients reached a clinical end point during a median 7 years (range 1-16 years) of follow-up. The 5-, 10- and 15-year adverse outcome-free survivals were 95%, 85%, and 77%. The GLOBE and UK-PBC scores predicted cirrhosis-related complications better than the UDCA response criteria. The hazard ratio (HR) for a 1 standard deviation increase was HR 5.05 (95% confidence interval (CI): 4.43-5.74, P < 0.001) for the GLOBE score and HR 3.39 (95% CI: 3.10-3.72, P < 0.001) for the UK-PBC score. Overall, the GLOBE and UK-PBC risk scores showed similar and excellent prognostic performance (C-statistic, 0.93; 95% CI: 0.91%-95% vs 0.94; 95% CI: 0.91%-0.96%). DISCUSSION: In our international, multicenter PBC cohort, the GLOBE and UK-PBC risk scoring systems were good predictors of future cirrhosis-related complications.
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| 38. |
- Esteban-Cornejo, Irene, et al.
(författare)
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Fitness, cortical thickness and surface area in overweight/obese children: The mediating role of body composition and relationship with intelligence
- 2019
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Ingår i: NeuroImage. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1053-8119 .- 1095-9572. ; 186, s. 771-781
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Tidskriftsartikel (refereegranskat)abstract
- Cortical thickness and surface area are thought to be genetically unrelated and shaped by independent neurobiological events suggesting that they should be considered separately in morphometric analyses. Although the developmental trajectories of cortical thickness and surface area may differ across brain regions and ages, there is no consensus regarding the relationships of physical fitness with cortical thickness and surface area as well as for its subsequent influence on intelligence. Thus, this study examines: (i) the associations of physical fitness components (i.e., cardiorespiratory fitness, speed-agility and muscular fitness) with overall and regional cortical thickness and surface area; (ii) whether body composition indicators (i.e., body mass index, fat-free mass index and fat mass index) mediate these associations; and (iii) the association of physical fitness and cortical thickness with intelligence in overweight/obese children. A total of 101 overweight/obese children aged 8-11 years were recruited in Granada, Spain. The physical fitness components were assessed following the ALPHA health-related fitness test battery. T1-weighted images were acquired with a 3.0 Tesla Siemens Magnetom Tim Trio system. We used FreeSurfer software version 5.3.0 to assess cortical thickness (mm) and surface area (mm(2)). The main results showed that cardiorespiratory fitness and speed-agility were related to overall cortical thickness (beta = 0.321 and beta = 0.302, respectively; both P amp;lt; 0.05), and in turn, cortical thickness was associated with higher intelligence (beta = 0.198, P amp;lt; 0.05). Muscular fitness was not related to overall cortical thickness. None of the three physical fitness components were related to surface area (p amp;gt; 0.05). The associations of cardiorespiratory fitness and speed-agility with overall cortical thickness were mediated by fat mass index (56.86% amp; 62.28%, respectively). In conclusion, cardiorespiratory fitness and speed-agility, but not muscular fitness, are associated with overall cortical thickness, and in turn, thicker brain cortex is associated with higher intelligence in overweight/obese children. Yet, none of the three physical fitness components were related to surface area. Importantly, adiposity may hinder the benefits of cardiorespiratory fitness and speed-agility on cortical thickness. Understanding individual differences in brain morphology may have important implications for educators and policy makers who aim to determine policies and interventions to maximize academic learning and occupational success later in life.
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| 41. |
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| 42. |
- Henriksson, Hanna, 1977-, et al.
(författare)
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Hip and wrist accelerometers showed consistent associations with fitness and fatness in children aged 8-12 years
- 2020
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Ingår i: Acta Paediatrica. - : WILEY. - 0803-5253 .- 1651-2227. ; 109:5, s. 995-1003
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Tidskriftsartikel (refereegranskat)abstract
- Aim Physical activity (PA) has traditionally been measured wearing accelerometers on the hip, but they are increasingly being worn on the wrist. We compared hip and wrist accelerometers with regard to their acceptability and any associations between PA and fatness and fitness. Methods This cross-sectional study comprised 103 children aged 8-12 years (62% boys) who participated in the ActiveBrains trial by the University of Granada, Spain, in 2014-2016. The children wore both ActiGraph GT3X+ hip and wrist accelerometers round the clock for 7 days. The acceptability of both placements was evaluated by a questionnaire, while the childrens fat mass index, waist circumference and cardiorespiratory fitness (CRF) were assessed. Results Wearing wrist accelerometers caused less disturbance, mainly because hip accelerometers caused more issues during the night. The measurements from both placements showed that lower PA levels were associated with fatness and that higher PA levels were associated with better CRF. Conclusion Both placements showed consistent results with regard to measuring associations between PA levels and fatness and fitness. However, wearing them on the wrist caused less discomfort at night. Future studies are needed to confirm the best placement for accelerometers during PA studies.
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- Henriksson,, Lars Eric, et al.
(författare)
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Determination of the Nitrogen-Fixing Capacity of Algae in Soil
- 1972
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Ingår i: Oikos. - : JSTOR. - 0030-1299 .- 1600-0706. ; 23:3, s. 420-423
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Tidskriftsartikel (refereegranskat)abstract
- A method to determine the potential of microbial nitrogen fixation in soils under aerobic conditions is described. Four different soil types were studied; loess, lime, mull and calcareous soil. The soil samples were collected in three different areas in Europe.
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- Henriksson, Patrik J. G., et al.
(författare)
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Unpacking factors influencing antimicrobial use in global aquaculture and their implication for management : a review from a systems perspective
- 2018
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Ingår i: Sustainability Science. - : Springer Science and Business Media LLC. - 1862-4065 .- 1862-4057. ; 13:4, s. 1105-1120
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Forskningsöversikt (refereegranskat)abstract
- Global seafood provides almost 20% of all animal protein in diets, and aquaculture is, despite weakening trends, the fastest growing food sector worldwide. Recent increases in production have largely been achieved through intensification of existing farming systems, resulting in higher risks of disease outbreaks. This has led to increased use of antimicrobials (AMs) and consequent antimicrobial resistance (AMR) in many farming sectors, which may compromise the treatment of bacterial infections in the aquaculture species itself and increase the risks of AMR in humans through zoonotic diseases or through the transfer of AMR genes to human bacteria. Multiple stakeholders have, as a result, criticized the aquaculture industry, resulting in consequent regulations in some countries. AM use in aquaculture differs from that in livestock farming due to aquaculture's greater diversity of species and farming systems, alternative means of AM application, and less consolidated farming practices in many regions. This, together with less research on AM use in aquaculture in general, suggests that large data gaps persist with regards to its overall use, breakdowns by species and system, and how AMs become distributed in, and impact on, the overall social-ecological systems in which they are embedded. This paper identifies the main factors (and challenges) behind application rates, which enables discussion of mitigation pathways. From a set of identified key mechanisms for AM usage, six proximate factors are identified: vulnerability to bacterial disease, AM access, disease diagnostic capacity, AMR, target markets and food safety regulations, and certification. Building upon these can enable local governments to reduce AM use through farmer training, spatial planning, assistance with disease identification, and stricter regulations. National governments and international organizations could, in turn, assist with disease-free juveniles and vaccines, enforce rigid monitoring of the quantity and quality of AMs used by farmers and the AM residues in the farmed species and in the environment, and promote measures to reduce potential human health risks associated with AMR.
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