| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Sampson, Joshua N., et al.
(författare)
-
Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
-
Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
-
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.
|
|
| 11. |
- Machiela, Mitchell J., et al.
(författare)
-
Characterization of Large Structural Genetic Mosaicism in Human Autosomes
- 2015
-
Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 96:3, s. 487-497
-
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.
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Jacobs, Kevin B, et al.
(författare)
-
Detectable clonal mosaicism and its relationship to aging and cancer.
- 2012
-
Ingår i: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658
-
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.
|
|
| 15. |
- Machiela, Mitchell J, et al.
(författare)
-
Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome
- 2016
-
Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 7
-
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.
|
|
| 16. |
|
|
| 17. |
- Wang, Zhaoming, et al.
(författare)
-
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
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
-
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.
|
|
| 18. |
|
|
| 19. |
- Migueles, Jairo H., et al.
(författare)
-
Effects of an Exercise Program on Cardiometabolic and Mental Health in Children With Overweight or Obesity A Secondary Analysis of a Randomized Clinical Trial
- 2023
-
Ingår i: JAMA Network Open. - : AMER MEDICAL ASSOC. - 2574-3805. ; 6:7
-
Tidskriftsartikel (refereegranskat)abstract
- Importance Childhood obesity is a risk factor associated with type 2 diabetes, cardiovascular disease, and mental disorders later in life. Investigation of the parallel effects of a defined exercise program on cardiometabolic and mental health in children with overweight or obesity may provide new insights on the potential benefits of exercise on overall health. Objective To investigate the effects of a 20-week exercise program on cardiometabolic and mental health in children with overweight or obesity. Design, Setting, and Participants This secondary analysis of a parallel-group randomized clinical trial was conducted in Granada, Spain, from November 1, 2014, to June 30, 2016. Data analyses were performed between February 1, 2020, and July 14, 2022. Children with overweight or obesity aged 8 to 11 years were eligible, and the study was performed in an out-of-school context. Intervention The exercise program included 3 to 5 sessions/wk (90 min/session) of aerobic plus resistance training for 20 weeks. The wait-list control group continued with their usual routines. Main Outcomes and Measures Cardiometabolic outcomes as specified in the trial protocol included body composition (fat mass, fat-free mass, and visceral adipose tissue), physical fitness (cardiorespiratory, speed-agility, and muscular), and traditional risk factors (waist circumference, blood lipid levels, glucose levels, insulin levels, and blood pressure). Cardiometabolic risk score (z score) was calculated based on age and sex reference values for levels of triglycerides, inverted high-density lipoprotein cholesterol, and glucose, the mean of systolic and diastolic blood pressure, and waist circumference. An additional cardiometabolic risk score also included cardiorespiratory fitness. Mental health outcomes included an array of psychological well-being and ill-being indicators. Results The 92 participants included in the per-protocol analyses (36 girls [39%] and 56 boys [61%]) had a mean (SD) age of 10.0 (1.1) years. The exercise program reduced the cardiometabolic risk score byapproximately0.38 (95% CI, -0.74 to -0.02) SDs; decreased low-density lipoprotein cholesterol level by -7.00 (95% CI, -14.27 to 0.37) mg/dL (to convert to mmol/L, multiply by 0.0259), body mass index (calculated as weight in kilograms divided by height in meters squared) by -0.59 (95% CI, -1.06 to -0.12), fat mass index by -0.67 (95% CI, -1.01 to -0.33), and visceral adipose tissue by -31.44 (95% CI, -58.99 to -3.90) g; and improved cardiorespiratory fitness by 2.75 (95% CI, 0.22-5.28) laps in the exercise group compared with the control group. No effects were observed on mental health outcomes. Conclusions and Relevance In this secondary analysis of a randomized clinical trial, an aerobic plus resistance exercise program improved cardiometabolic health in children with overweight or obesity but had no effect on mental health.
|
|
| 20. |
- Nystrom, C. D., et al.
(författare)
-
Mobile-based intervention intended to stop obesity in preschool-aged children: the MINISTOP randomized controlled trial
- 2017
-
Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 105:6, s. 1327-1335
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Traditional obesity prevention programs are time-and cost-intensive. Mobile phone technology has been successful in changing behaviors and managing weight; however, to our knowledge, its potential in young children has yet to be examined. Objective: We assessed the effectiveness of a mobile health (mHealth) obesity prevention program on body fat, dietary habits, and physical activity in healthy Swedish children aged 4.5 y. Design: From 2014 to 2015, 315 children were randomly assigned to an intervention or control group. Parents in the intervention group received a 6-mo mHealth program. The primary outcome was fat mass index (FMI), whereas the secondary outcomes were intakes of fruits, vegetables, candy, and sweetened beverages and time spent sedentary and in moderate-to-vigorous physical activity. Composite scores for the primary and secondary outcomes were computed. Results: No statistically significant intervention effect was observed for FMI between the intervention and control group (mean +/- SD: -0.23 +/- 0.56 compared with -0.20 +/- 0.49 kg/m(2)). However, the intervention group increased their mean composite score from baseline to follow-up, whereas the control group did not (+ 0.36 +/- 1.47 compared with -0.06 +/- 1.33 units; P = 0.021). This improvement was more pronounced among the children with an FMI above the median (4.11 kg/m(2)) (P = 0.019). The odds of increasing the composite score for the 6 dietary and physical activity behaviors were 99% higher for the intervention group than the control group (P = 0.008). Conclusions: This mHealth obesity prevention study in preschool-aged children found no difference between the intervention and control group for FMI. However, the intervention group showed a considerably higher postintervention composite score (a secondary outcome) than the control group, especially in children with a higher FMI. Further studies targeting specific obesity classes within preschool-aged children are warranted.
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
- Berglund, U. W., et al.
(författare)
-
Validation and development of MTH1 inhibitors for treatment of cancer
- 2016
-
Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 27:12, s. 2275-2283
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Previously, we showed cancer cells rely on the MTH1 protein to prevent incorporation of otherwise deadly oxidised nucleotides into DNA and we developed MTH1 inhibitors which selectively kill cancer cells. Recently, several new and potent inhibitors of MTH1 were demonstrated to be non-toxic to cancer cells, challenging the utility of MTH1 inhibition as a target for cancer treatment. Material and methods: Human cancer cell lines were exposed in vitro to MTH1 inhibitors or depleted of MTH1 by siRNA or shRNA. 8-oxodG was measured by immunostaining and modified comet assay. Thermal Proteome profiling, proteomics, cellular thermal shift assays, kinase and CEREP panel were used for target engagement, mode of action and selectivity investigations of MTH1 inhibitors. Effect of MTH1 inhibition on tumour growth was explored in BRAF V600E-mutated malignant melanoma patient derived xenograft and human colon cancer SW480 and HCT116 xenograft models. Results: Here, we demonstrate that recently described MTH1 inhibitors, which fail to kill cancer cells, also fail to introduce the toxic oxidized nucleotides into DNA. We also describe a new MTH1 inhibitor TH1579, (Karonudib), an analogue of TH588, which is a potent, selective MTH1 inhibitor with good oral availability and demonstrates excellent pharmacokinetic and anti-cancer properties in vivo. Conclusion: We demonstrate that in order to kill cancer cells MTH1 inhibitors must also introduce oxidized nucleotides into DNA. Furthermore, we describe TH1579 as a best-in-class MTH1 inhibitor, which we expect to be useful in order to further validate the MTH1 inhibitor concept.
|
|
| 25. |
- Bjermer, Leif, et al.
(författare)
-
Radiation-induced increase in hyaluronan and fibronectin in bronchoalveolar lavage fluid from breast cancer patients is suppressed by smoking
- 1992
-
Ingår i: European Respiratory Journal. - 1399-3003. ; 5:7, s. 785-790
-
Tidskriftsartikel (refereegranskat)abstract
- Bronchoalveolar lavage (BAL) fluid was analysed from 21 patients with breast cancer, stage T1N0M0, who had undergone tumour resection and post-operative local irradiation (accumulated dose 56 Gy). The lavage was performed two months after radiotherapy, in the anterior part of the lingula (left side) or of the right middle lobe (right side), depending on which side had been exposed to radiation. The patients had significantly increased concentrations of fibronectin (FN) (p less than 0.001), hyaluronan (HA) (p less than 0.01) and albumin (p less than 0.05) in BAL fluid compared with the healthy controls (n = 19). However, when the patients were separated, according to smoking history, it was obvious that the inflammatory reaction occurred entirely in the nonsmoking patient group (n = 10), whilst no difference could be found between the smoking patients (n = 11) and the controls. In the nonsmoking patient group, there was a sevenfold increase in BAL concentrations of FN and a threefold increase in HA. Moreover, four patients had detectable levels of procollagen III peptide in BAL, all were nonsmokers. The smoking habits of the controls had no influence on the BAL measurements. These findings indicate that smoking interferes with the radiation-induced early inflammatory connective tissue reaction of the lung. Finally, the results justify further investigation of interaction of smoking with cancer treatment, both from the view of therapy effectiveness and reduction of adverse effects.
|
|
| 26. |
|
|
| 27. |
- Capala, J, et al.
(författare)
-
Boron neutron capture therapy for glioblastoma multiforme : Clinical studies in Sweden
- 2003
-
Ingår i: Journal of Neuro-Oncology. - 1573-7373. ; 62:1, s. 135-144
-
Tidskriftsartikel (refereegranskat)abstract
- A boron neutron capture therapy (BNCT) facility has been constructed at Studsvik, Sweden. It includes two filter/moderator configurations. One of the resulting neutron beams has been optimized for clinical irradiations with a filter/moderator system that allows easy variation of the neutron spectrum from the thermal to the epithermal energy range. The other beam has been designed to produce a large uniform field of thermal neutrons for radio-biological research. Scientific operations of the Studsvik BNCT project are overseen by the Scientific Advisory Board comprised of representatives of major universities in Sweden. Furthermore, special task groups for clinical and preclinical studies have been formed to facilitate collaboration with academia. The clinical Phase II trials for glioblastoma are sponsored by the Swedish National Neuro-Oncology Group and, presently, involve a protocol for BNCT treatment of glioblastoma patients who have not received any therapy other than surgery. In this protocol, p-boronophenylalanine (BPA), administered as a 6-h intravenous infusion, is used as the boron delivery agent. As of January 2002, 17 patients were treated. The 6-h infusion of 900 mg BPA/kg body weight was shown to be safe and resulted in the average blood-boron concentration of 24 μg/g (range: 15-32 μg/g) at the time of irradiation (approximately 2-3 h post-infusion). Peak and average weighted radiation doses to the brain were in the ranges of 8.0-15.5 Gy(W) and 3.3-6.1 Gy(W), respectively. So far, no severe BNCT-related acute toxicities have been observed. Due to the short follow-up time, it is too early to evaluate the efficacy of these studies.
|
|
| 28. |
- Delisle, C., et al.
(författare)
-
A web- and mobile phone-based intervention to prevent obesity in 4-year-olds (MINISTOP): a population-based randomized controlled trial
- 2015
-
Ingår i: Bmc Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 15
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Childhood obesity is an increasing health problem globally. Overweight and obesity may be established as early as 2-5 years of age, highlighting the need for evidence-based effective prevention and treatment programs early in life. In adults, mobile phone based interventions for weight management (mHealth) have demonstrated positive effects on body mass, however, their use in child populations has yet to be examined. The aim of this paper is to report the study design and methodology of the MINSTOP (Mobile-based Intervention Intended to Stop Obesity in Preschoolers) trial. Methods/Design: A two-arm, parallel design randomized controlled trial in 300 healthy Swedish 4-year-olds is conducted. After baseline measures, parents are allocated to either an intervention-or control group. The 6-month mHealth intervention consists of a web-based application (the MINSTOP app) to help parents promote healthy eating and physical activity in children. MINISTOP is based on the Social Cognitive Theory and involves the delivery of a comprehensive, personalized program of information and text messages based on existing guidelines for a healthy diet and active lifestyle in pre-school children. Parents also register physical activity and intakes of candy, soft drinks, vegetables as well as fruits of their child and receive feedback through the application. Primary outcomes include body fatness and energy intake, while secondary outcomes are time spent in sedentary, moderate, and vigorous physical activity, physical fitness and intakes of fruits and vegetables, snacks, soft drinks and candy. Food and energy intake (Tool for Energy balance in Children, TECH), body fatness (pediatric option for BodPod), physical activity (Actigraph wGT3x-BT) and physical fitness (the PREFIT battery of five fitness tests) are measured at baseline, after the intervention (six months after baseline) and at follow-up (12 months after baseline). Discussion: This novel study will evaluate the effectiveness of a mHealth program for mitigating gain in body fatness among 4-year-old children. If the intervention proves effective it has great potential to be implemented in child-health care to counteract childhood overweight and obesity.
|
|
| 29. |
|
|
| 30. |
- Henriksson, Hanna, et al.
(författare)
-
Cardiorespiratory fitness, muscular strength, and obesity in adolescence and later chronic disability due to cardiovascular disease: a cohort study of 1 million men
- 2020
-
Ingår i: European Heart Journal. - : OXFORD UNIV PRESS. - 0195-668X .- 1522-9645. ; 41:15, s. 1503-
-
Tidskriftsartikel (refereegranskat)abstract
- Aims Cardiorespiratory fitness, muscular strength, and obesity in adulthood are risk factors for cardiovascular disease (CVD). However, Little is known regarding the associations of these risk factors, already in adolescence, with later disability due to chronic CVD. Hence, we investigated associations of cardiorespiratory fitness, muscular strength, and body mass index (BMI) in adolescence with Later chronic disability due to specific causes of CVD disability (i.e. cerebrovascutar disease, ischaemic heart disease and heart failure). Methods and results This population-based cohort study included 1 078 685 male adolescents (16-19 years) from the Swedish military conscription register from 1972 to 1994. Cardiorespiratory fitness (bicycle ergometer test), muscular strength (knee extension strength), and BMI were measured during the conscription examination. Information about disability pension due to CVD was retrieved from the Social Insurance Agency during a mean follow-up of 28.4 years. Cardiorespiratory fitness was strongly and inversely associated with later risk of chronic CVD disability for all investigated causes. The association was particularly strong for ischaemic heart diseases (hazard ratio 0.11, 95% confidence interval 0.05-0.29 for highest vs. lowest fitness-quintiles). Furthermore, overweight/obesity were associated with CVD disability for all investigated causes. Conversely, associations of muscular strength with CVD disability were generally weak. Conclusions This study provides evidence for associations between low levels of cardiorespiratory fitness and obesity with later risk of chronic disability due to CVD. Preventive actions may begin at young ages and include promotion of cardiorespiratory fitness and healthy body weight.
|
|
| 31. |
- Henriksson, Hanna, et al.
(författare)
-
Longitudinal Physical Activity, Body Composition, and Physical Fitness in Preschoolers
- 2017
-
Ingår i: Medicine & Science in Sports & Exercise. - : LIPPINCOTT WILLIAMS & WILKINS. - 0195-9131 .- 1530-0315. ; 49:10, s. 2078-2085
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: This study aimed to investigate longitudinal associations of objectively measured physical activity (PA) and sedentary behavior (SB) with body composition and physical fitness at a 12-month follow-up in healthy Swedish 4-yr-old children. Methods: The data from the population-based MINISTOP trial were collected between 2014 and 2016, and this study included the 138 children who were in the control group. PA and SB were assessed using the wrist-worn ActiGraph (wGT3x-BT) accelerometer during seven 24-h periods and, subsequently, defined as SB, light-intensity PA, moderate-intensity PA, vigorous-intensity PA (VPA), and moderate-to-vigorous PA (MVPA). Body composition was measured using air-displacement plethysmography and physical fitness (cardiorespiratory fitness, lower and upper muscular strength as well as motor fitness) by the PREFIT fitness battery. Linear regression and isotemporal substitution models were applied. Results: Greater VPA and MVPA at the age of 4.5 yr were associated with higher fat-free mass index (FFMI) at 5.5 yr (P amp;lt; 0.001 and P = 0.044, respectively). Furthermore, greater VPA and MVPA at the age of 4.5 yr were associated with higher scores for cardiorespiratory fitness, lower body muscular strength, and motor fitness at 12-month follow-up (P = 0.001 to P = 0.031). Substituting 5 min.d(-1) of SB, light-intensity PA, or moderate-intensity PA for VPA at the age of 4.5 yr were associated with higher FFMI, and with greater upper and lower muscular strength at 12-month follow-up (P amp;lt; 0.001 to P = 0.046). Conclusion: Higher VPA and MVPA at the age of 4.5 yr were significantly associated with higher FFMI and better physical fitness at 12-month follow-up. Our results indicate that promoting high-intensity PA at young ages may have long-term beneficial effects on childhood body composition and physical fitness, in particular muscular strength.
|
|
| 32. |
|
|
| 33. |
- Henriksson, Pontus, 1982-, et al.
(författare)
-
Physical fitness in relation to later body composition in pre-school children
- 2019
-
Ingår i: Journal of Science and Medicine in Sport. - : Elsevier. - 1440-2440 .- 1878-1861. ; 22:5, s. 574-579
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectivesAlthough physical fitness is considered a marker of health in youth, little is known whether physical fitness in pre-school age is related to later body composition. Thus, this study investigated (i) associations of physical fitness at 4.5 years of age with body composition 12 months later and (ii) whether improvements in physical fitness during the 12-month follow-up were associated with changes in body composition.DesignThis study included 142 children, measured at 4.5 and 5.5 years, from the control group of the MINISTOP trial.MethodsPhysical fitness (cardiorespiratory fitness, lower- and upper-body muscular strength and motor fitness) was measured using the PREFIT test battery. Body composition was assessed using air-displacement plethysmography.ResultsIn adjusted regression analyses, greater cardiorespiratory fitness, lower-body muscular strength and motor fitness at 4.5 years were associated with a lower fat mass index at 5.5 years (standardized β= −0.182 to −0.229, p ≤ 0.028). Conversely, greater cardiorespiratory fitness, lower- and upper-body muscular strength as well as motor fitness at 4.5 years of age were associated with a higher fat-free mass index (standardized β = 0.255–0.447, p ≤ 0.001). Furthermore, improvements in cardiorespiratory fitness, lower-body muscular strength and motor fitness during the 12-month follow-up period were associated with decreases in fat mass index and/or % fat mass.ConclusionsIn conclusion, the results of this study provide evidence of the importance of physical fitness early in life. Nevertheless, further studies are needed in order to clarify the influence of physical fitness in the pre-school age with later health outcomes.
|
|
| 34. |
|
|
| 35. |
|
|
| 36. |
- Ladds, Marcus J. G. W., et al.
(författare)
-
A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage
- 2018
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- The development of non-genotoxic therapies that activate wild-type p53 in tumors is of great interest since the discovery of p53 as a tumor suppressor. Here we report the identification of over 100 small-molecules activating p53 in cells. We elucidate the mechanism of action of a chiral tetrahydroindazole (HZ00), and through target deconvolution, we deduce that its active enantiomer (R)-HZ00, inhibits dihydroorotate dehydrogenase (DHODH). The chiral specificity of HZ05, a more potent analog, is revealed by the crystal structure of the (R)-HZ05/DHODH complex. Twelve other DHODH inhibitor chemotypes are detailed among the p53 activators, which identifies DHODH as a frequent target for structurally diverse compounds. We observe that HZ compounds accumulate cancer cells in S-phase, increase p53 synthesis, and synergize with an inhibitor of p53 degradation to reduce tumor growth in vivo. We, therefore, propose a strategy to promote cancer cell killing by p53 instead of its reversible cell cycle arresting effect.
|
|
| 37. |
- Ladds, MJGW, et al.
(författare)
-
Publisher Correction: A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage
- 2018
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 2071-
-
Tidskriftsartikel (refereegranskat)abstract
- The original PDF version of this Article listed the authors as “Marcus J.G.W. Ladds,” where it should have read “Marcus J. G. W. Ladds, Ingeborg M. M. van Leeuwen, Catherine J. Drummond et al.#”.Also in the PDF version, it was incorrectly stated that “Correspondence and requests for materials should be addressed to S. Lín.”, instead of the correct “Correspondence and requests for materials should be addressed to S. Laín.”This has been corrected in the PDF version of the Article. The HTML version was correct from the time of publication.
|
|
| 38. |
|
|
| 39. |
|
|
| 40. |
|
|
| 41. |
|
|
| 42. |
|
|
| 43. |
- Michel, M., et al.
(författare)
-
Small-molecule activation of OGG1 increases oxidative DNA damage repair by gaining a new function
- 2022
-
Ingår i: Science. - Stockholm : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 376:6600, s. 1471-1476
-
Tidskriftsartikel (refereegranskat)abstract
- Oxidative DNA damage is recognized by 8-oxoguanine (8-oxoG) DNA glycosylase 1 (OGG1), which excises 8-oxoG, leaving a substrate for apurinic endonuclease 1 (APE1) and initiating repair. Here, we describe a small molecule (TH10785) that interacts with the phenylalanine-319 and glycine-42 amino acids of OGG1, increases the enzyme activity 10-fold, and generates a previously undescribed b,d-lyase enzymatic function. TH10785 controls the catalytic activity mediated by a nitrogen base within its molecular structure. In cells, TH10785 increases OGG1 recruitment to and repair of oxidative DNA damage. This alters the repair process, which no longer requires APE1 but instead is dependent on polynucleotide kinase phosphatase (PNKP1) activity. The increased repair of oxidative DNA lesions with a small molecule may have therapeutic applications in various diseases and aging. © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works
|
|
| 44. |
- Möller, Páll H., et al.
(författare)
-
Interstitial laser thermotherapy : Comparison between bare fibre and sapphire probe
- 1995
-
Ingår i: Lasers in Medical Science. - 0268-8921. ; 10:3, s. 193-200
-
Tidskriftsartikel (refereegranskat)abstract
- A sapphire probe and a bare fibre were compared with respect to temperature control and distribution and light fluence in interstitial laser thermotherapy. Experiments were performed in processed liver using an Nd-YAG laser and output power levels of 1-4 W. The temperature was controlled at a distance of 10 mm using a feedback circuit with an automatic thermometry system and thermistor probes. With the sapphire probe, carbonization was rare at power levels of 1-2 W but was observed in half of the experiments at 3 W and in all experiments at 4 W. Using the bare fibre, carbonization was seen in almost all experiments. Absence of carbonization was associated with a moderate decrease in the penetration of light and excellent control of the temperature, whereas carbonization led to rapid impairment of light penetration and temperature control. In addition, the temperature gradient was smaller with the sapphire probe than with the bare fibre or when carbonization was absent. It is concluded that a diffuser tip, such as the sapphire probe, may be preferable to the bare fibre for interstitial laser thermotherapy because it gives a smaller temperature gradient and helps to avoid carbonization which results in preserved light penetration and improved temperature control.
|
|
| 45. |
- Möller, P. H., et al.
(författare)
-
Temperature control and light penetration in a feedback interstitial laser thermotherapy system
- 1996
-
Ingår i: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 12:1, s. 49-63
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to describe the performance of a closed loop interstitial laser thermotherapy system in processed liver and to demonstrate its suitability for treating a vascularized tumour in vivo. The thermotherapy system consisted of an Nd:YAG laser and a temperature feedback circuit including an automatic thermometry system and thermistor probes. Experiments in processed liver were performed with a sapphire probe and temperature control at a distance of 10 mm. In most experiments at 1-2 W, and in half of the experiments at 3 W, there was no carbonization, a moderate change in the light penetration and excellent control of the temperature. In experiments with output powers of 4-5 W there was carbonization with rapid deterioration of light penetration and impaired control of the temperature. Carbonization affected the distribution of temperatures, which were lower below, and higher above, the laser tip in experiments with carbonization as compared to experiments without carbonization. Treatment of an adenocarcinoma implanted into rat liver was performed at 2 W with a bare fibre and without blood inflow occlusion. The feedback thermistor probe was placed 3 mm outside the margin of the tumour (largest diameter 9.5 ± 0.3 mm (mean ± SEM)). Temperature control and light penetration characteristics were similar to those found in vitro. No tumour could be demonstrated at sacrifice 6 days later. It is concluded that a closed loop feedback system can produce stable and reproducible local hyperthermia, that it performs better when carbonization is avoided and light penetration is preserved and that it has a great potential for interstitial thermotherapy of malignant tumours.
|
|
| 46. |
- Mörtzell Henriksson, Monica, et al.
(författare)
-
Adverse events in apheresis : an update of the WAA registry data
- 2016
-
Ingår i: Transfusion and apheresis science. - : Elsevier. - 1473-0502 .- 1878-1683. ; 54:1, s. 2-15
-
Forskningsöversikt (refereegranskat)abstract
- Apheresis with different procedures and devices are used for a variety of indications that may have different adverse events (AEs). The aim of this study was to clarify the extent and possible reasons of various side effects based on data from a multinational registry. The WAA-apheresis registry data focus on adverse events in a total of 50846 procedures in 7142 patients (42% women). AEs were graded as mild, moderate (need for medication), severe (interruption due to the AE) or death (due to AE). More AEs occurred during the first procedures versus subsequent (8.4 and 5.5%, respectively). AEs were mild in 2.4% (due to access 54%, device 7%, hypotension 15%, tingling 8%), moderate in 3% (tingling 58%, urticaria 15%, hypotension 10%, nausea 3%), and severe in 0.4% of procedures (syncope/hypotension 32%, urticaria 17%, chills/fever 8%, arrhythmia/asystole 4.5%, nausea/vomiting 4%). Hypotension was most common if albumin was used as the replacement fluid, and urticaria when plasma was used. Arrhythmia occurred to similar extents when using plasma or albumin as replacement. In 64% of procedures with bronchospasm, plasma was part of the replacement fluid used. Severe AEs are rare. Although most reactions are mild and moderate, several side effects may be critical for the patient. We present side effects in relation to the procedures and suggest that safety is increased by regular vital sign measurements, cardiac monitoring and by having emergency equipment nearby.
|
|
| 47. |
|
|
| 48. |
|
|
| 49. |
|
|
| 50. |
|
|
