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Sökning: WFRF:(Lampa Erik 1977 )

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1.
  • Lind, Lars, et al. (författare)
  • Longitudinal effects of aging on plasma proteins levels in older adults - associations with kidney function and hemoglobin levels
  • 2019
  • Ingår i: ; 14:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Background A targeted proteomics chip has been shown to be useful to discover novel associations of proteins with cardiovascular disease. We investigated how these proteins change with aging, and whether this change is related to a decline in kidney function, or to a change in hemoglobin levels. Material and methods In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, including 1,016 participants from the general population aged 70 at baseline, 84 proteins were measured at ages 70, 75, 80. At these occasions, glomerular filtration rate (eGFR) was estimated and the hemoglobin levels were measured. Results Sixty-one of the 84 evaluated proteins changed significantly during the 10-year follow-up (multiple testing-adjusted alpha = 0.00059), most showing an increase. The change in eGFR was inversely related to changes of protein levels for the vast majority of proteins (74%). The change in hemoglobin was significantly related to the change in 40% of the evaluated proteins, with no obvious preference of the direction of these relationships. Conclusion The majority of evaluated proteins increased with aging in adults. Therefore, normal ranges for proteins might be given in age-strata. The increase in protein levels was associated with the degree of reduction in eGFR for the majority of proteins, while no clear pattern was seen for the relationships between the proteins and the change in hemoglobin levels. Studies on changes in urinary proteins are warranted to understand the association between the reduction in eGFR and increase in plasma protein levels.
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2.
  • Wang, Yunzhang, et al. (författare)
  • Epigenetic influences on aging : a longitudinal genome-wide methylation study in old Swedish twins
  • 2018
  • Ingår i: ; 13:9, s. 975-987
  • Tidskriftsartikel (refereegranskat)abstract
    • Age-related changes in DNA methylation were observed in cross-sectional studies, but longitudinal evidence is still limited. Here, we aimed to characterize longitudinal age-related methylation patterns using 1011 blood samples collected from 385 Swedish twins (age at entry: mean 69 and standard deviation 9.7, 73 monozygotic and 96 dizygotic pairs) up to five times (mean 2.6) over 20 years (mean 8.7). We identified 1316 age-associated methylation sites (P<1.3x10(-7)) using a longitudinal epigenome-wide association study design. We measured how estimated cellular compositions changed with age and how much they confounded the age effect. We validated the results in two independent longitudinal cohorts, where 118 CpGs were replicated in Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, 390 samples) (P<3.9x10(-5)), 594 in Lothian Birth Cohort (LBC, 3018 samples) (P<5.1x10(-5)) and 63 in both. Functional annotation of age-associated CpGs showed enrichment in CCCTC-binding factor (CTCF) and other transcription factor binding sites. We further investigated genetic influences on methylation and found no interaction between age and genetic effects in the 1316 age-associated CpGs. Moreover, in the same CpGs, methylation differences within twin pairs increased with 6.4% over 10 years, where monozygotic twins had smaller intra-pair differences than dizygotic twins. In conclusion, we show that age-related methylation changes persist in a longitudinal perspective, and are fairly stable across cohorts. The changes are under genetic influence, although this effect is independent of age. Moreover, methylation variability increase over time, especially in age-associated CpGs, indicating the increase of environmental contributions on DNA methylation with age.
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3.
  • Gustafsson, Sofia, et al. (författare)
  • Heterogeneous drug tissue binding in brain regions of rats, Alzheimer’s patients and controls : impact on translational drug development
  • 2019
  • Ingår i: Scientific Reports. - 2045-2322 .- 2045-2322. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • For preclinical and clinical assessment of therapeutically relevant unbound, free, brain concentrations, the pharmacokinetic parameter fraction of unbound drug in brain (fu,brain) is commonly used to compensate total drug concentrations for nonspecific brain tissue binding (BTB). As, homogenous BTB is assumed between species and in health and disease, rat BTB is routinely used. The impact of Alzheimer’s disease (AD) on drug BTB in brain regions of interest (ROI), i.e., fu,brain,ROI, is yet unclear. This study for the first time provides insight into regional drug BTB and the validity of employing rat fu,brain,ROI as a surrogate of human BTB, by investigating five marketed drugs in post-mortem tissue from AD patients (n = 6) and age-matched controls (n = 6). Heterogeneous drug BTB was observed in all within group comparisons independent of disease and species. The findings oppose the assumption of uniform BTB, highlighting the need of case-by-case evaluation of fu,brain,ROI in translational CNS research.
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4.
  • Högberg, Ulf, 1949-, et al. (författare)
  • Infant abuse diagnosis associated with abusive head trauma criteria : incidence increase due to overdiagnosis?
  • 2018
  • Ingår i: European Journal of Public Health. - : OXFORD UNIV PRESS. - 1101-1262 .- 1464-360X. ; 28:4, s. 641-646
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The hypothesis of this study is that the diagnosis of infant abuse is associated with criteria for shaken baby syndrome (SBS)/abusive head trauma (AHT), and that that changes in incidence of abuse diagnosis in infants may be due to increased awareness of SBS/AHT criteria.Methods: This was a population-based register study. Setting: Register study using the Swedish Patient Register, Medical Birth Register, and Cause of Death Register. The diagnosis of infant abuse was based on the International Classification of Diseases, 9th and 10th revision. Participants: All children born in Sweden during 1987-2014 with a follow-up until 1 year of age (N = 2 868 933). SBS/AHT criteria: subdural haemorrhage, cerebral contusion, skull fracture, convulsions, retinal haemorrhage, fractures rib and long bones. Outcomes: Incidence, rate ratios, aetiologic fractions and Probit regression analysis.Results: Diagnosis of infant abuse was strongly associated with SBS/AHT criteria, but not risk exposure as region, foreign-born mother, being born preterm, multiple birth and small for gestational age. The incidence of infant abuse has increased tenfold in Sweden since the 1990s and has doubled since 2008, from 12.0 per 100 000 infants during 1997-2007 to 26.5/100 000 during 2008-2014, with pronounced regional disparities.Conclusions: Diagnosis of infant abuse is related to SBS/AHT criteria. The increase in incidence coincides with increased medical preparedness to make a diagnosis of SBS/AHT. Hidden statistics and a real increase in abuse are less plausible. Whether the increase is due to overdiagnosis cannot be answered with certainty, but the possibility raises ethical and medico-legal concerns.
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5.
  • Lind, Lars, et al. (författare)
  • Impact of Aging on the Strength of Cardiovascular Risk Factors : A Longitudinal Study Over 40 Years
  • 2018
  • Ingår i: ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background-The knowledge of the impact of cardiovascular risk factors at different ages has mainly been based on different studies performed at different ages. This study aimed to investigate the change in impact of traditional cardiovascular risk factors over the aging process in subjects followed for 4 decades. Methods and Results-In the ULSAM (Uppsala Longitudinal Study of Adult Men) study, 2322 men originally investigated in 1970 to 1974 have been followed regarding cardiovascular diseases until the end of 2013. This cohort has been investigated physically at ages 50, 60, 70, 77, and 82 years regarding body mass index, low-density lipoprotein-and high-density lipoprotein-cholesterol, triglycerides, systolic blood pressure and diastolic blood pressure, fasting glucose, and smoking. These data were used to model the interactions between risk factors and age regarding incident myocardial infarction (n=540), ischemic stroke (n=343), or heart failure (n=397). Significant interactions were observed between age and the set of traditional risk factors regarding all 3 outcomes (P<0.05 for all). Generally, a decline in the rate ratios was seen with aging for most risk factors, being most pronounced for body mass index regarding myocardial infarction and for systolic blood pressure regarding ischemic stroke and heart failure. However, low-density lipoprotein-cholesterol was significantly related to incident myocardial infarction, whereas both body mass index and fasting glucose were significantly related to incident heart failure also at a high age. Conclusions-Using a longitudinal design in middle-aged men spanning 4 decades showed that the impact of traditional cardiovascular risk factors generally declined with aging. However, some of the risk factors remained significantly associated with incident cardiovascular disease also at old age.
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6.
  • Lind, Lars, et al. (författare)
  • Methylation-based estimated biological age and cardiovascular disease
  • 2018
  • Ingår i: ; 48:2
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: DNA methylation changes over life at specific sites in the genome, which can be used to estimate "biological age." The aim of this population-based longitudinal cohort study was to investigate the association between estimated biological age and incident cardiovascular disease (CVD).MATERIALS AND METHODS: Based on formulas published by Hannum et al and Horvath et al, "biological age" was calculated using data from the Illumina 450k Bead Methylation chip in 832 participants free from cardiovascular disease in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study (50% women, all aged 70 years at the examination). The difference between estimated biological and chronological age was calculated (DiffAge).RESULTS: During 10 years of follow-up, 153 incident cases of cardiovascular disease occurred. In the sex-adjusted analyses, the Horvath estimation of DiffAge was significantly related to incident cardiovascular disease (HR 1.040, 95% CI 1.010-1.071, P = .0079). Thus, for each year of increased biological age, a 4% increased risk of future cardiovascular disease was observed. This relationship was still significant following adjustment for the traditional risk factors sex, BMI, diabetes, HDL and LDL-cholesterol, systolic blood pressure and smoking (HR 1.033, 95% CI 1.004-1.063, P = .024). No such significant association was found using the Hannum formula.CONCLUSIONS: DNA methylation-based estimation of "biological age" per Horvath was associated with incident cardiovascular disease.
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7.
  • Lind, Lars, et al. (författare)
  • The Interplay Between Fat Mass and Fat Distribution as Determinants of the Metabolic Syndrome Is Sex-Dependent
  • 2017
  • Ingår i: ; 15:7, s. 337-343
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Fat mass and fat distribution are major determinants of the metabolic syndrome (MetS), but the interplay between them has not been thoroughly investigated. In addition, fat mass and fat distribution are generally different in men than in women. We aimed to determine whether the interplay between fat mass and fat distribution regarding MetS and its components is sex-dependent using data from the large-scale population-based sample EpiHealth. Methods: Occurrence of MetS and its components was determined together with fat mass by bioimpedance in 19,094 participants in the EpiHealth sample [mean age 61 years (SD 8.5), 56% females]. MetS was defined by the NCEP/ATPIII-criteria. Results: MetS prevalence was 23.0%. Fat mass (percent of body weight) was more strongly related to MetS (and the number of MetS components) in men than in women (P<0.0001 for interaction term) and in those with a high compared with those with a low waist/hip ratio (WHR). This modulating effect of WHR on the fat mass versus MetS-relationship was more pronounced in women than in men (P<0.0001 for interaction term). When analyzing the MetS components one by one, fat mass was more closely related to all the individual MetS criteria in men than in women, except for the glucose criteria. Conclusions: Fat mass is more closely related to prevalent MetS in men than in women, but the modulating effect of an abdominal type of fat distribution on the fat mass versus MetS-relationship is stronger in women.
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8.
  • Lindström, Linda, 1978-, et al. (författare)
  • Growth patterns during early childhood in children born small for gestational age and moderate preterm
  • 2019
  • Ingår i: ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Today we lack knowledge if size at birth and gestational age interacts regarding postnatal growth pattern in children born at 32 gestational weeks or later.This population-based cohort study comprised 41,669 children born in gestational weeks 32-40 in Uppsala County, Sweden, between 2000 and 2015. We applied a generalized least squares model including anthropometric measurements at 1.5, 3, 4 and 5 years. We calculated estimated mean height, weight and BMI for children born in week 32+0, 35+0 or 40+0 with birthweight 50th percentile (standardized appropriate for gestational age, sAGA) or 3rd percentile (standardized small for gestational age, sSGA).Compared with children born sAGA at gestational week 40+0, those born sAGA week 32+0 or 35+0 had comparable estimated mean height, weight and BMI after 3 years of age. Making the same comparison, those born sSGA week 32+0 or 35+0 were shorter and lighter with lower estimated mean BMI throughout the whole follow-up period.Our findings suggest that being born SGA and moderate preterm is associated with short stature and low BMI during the first five years of life. The association seemed stronger the shorter gestational age at birth.
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9.
  • Mocumbi, Sibone, et al. (författare)
  • Mothers' satisfaction with care during facility-based childbirth : a cross-sectional survey in southern Mozambique
  • 2019
  • Ingår i: BMC Pregnancy and Childbirth. - : BMC. - 1471-2393 .- 1471-2393. ; 19:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Client satisfaction is an essential component of quality of care. Health system factors, processes of care as well as mothers' characteristics influence the extent to which care meets the expectations of mothers and families. In our study, we specifically aimed to address the mothers' experiences of, and satisfaction with, care during childbirth. Methods A population-based cross-sectional study, using structured interviews with published sequences of questions assessing satisfaction, including 4358 mothers who gave birth during the 12 months before June 2016 to estimate satisfaction with childbirth care. Regression analysis was used to determine the predictors of client satisfaction. Results Most mothers (92.5%) reported being satisfied with care during childbirth and would recommend that a family member to deliver at the same facility. Specifically, 94.7% were satisfied with the cleanliness of the facility, 92.0% reported being satisfied with the interaction with the healthcare providers, but only 49.8% felt satisfied with the assistance to feed their baby. Mothers who had negative experiences during the process of care, such as being abandoned when needing help, disrespect, humiliation, or physical abuse, reported low levels of satisfaction when compared to those who had not had such experiences (68.5% vs 93.5%). Additionally, they reported higher levels of dissatisfaction (20.1% vs 2.1%). Regression analysis revealed that mothers who gave birth in primary level facilities tended to be more satisfied than those who gave birth in hospitals, and having a companion increased, on average, the overall satisfaction score, with 0.06 in type II health centres (CI 0.03-0.10) and with 0.05 in type I health centres (CI - 0.02 - 0.13), compared to - 0.01(CI -0.08 - 0.07) in the hospitals, irrespective of age, education and socio-economic background. Conclusion Childbirth at the primary level facilities contributes to the level of satisfaction. The provision of childbirth care should consider women's preferences and needs, including having a companion of choice. We highlight the challenge in balancing safety of care versus satisfaction with care and in developing policies on the optimum configuration of childbirth care. Interventions to improve the interaction with providers and the provision of respectful care are recommended.
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10.
  • Sundström, Johan, Professor, 1971-, et al. (författare)
  • Weight gain and blood pressure
  • 2020
  • Ingår i: ; 38:3, s. 387-394
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Although the causality of the obesity—hypertension association is established, the potential for prevention is not. We hypothesized that weight gain between early adulthood and mid-life is associated with higher mid-life blood pressure.METHODS: We investigated the hypothesis using a large contemporaneous population-based mid-life cohort of men and women aged 50-64 years. Recalled body weight at age 20 years was self-reported, and mid-life body weight and office blood pressures were measured in accordance with a detailed protocol.RESULTS: On average, men had gained 14.9 (95% CI 14.6-15.2) kg of weight, and women 14.6 (95% CI 14.4-14.9) kg, between age 20 years and the mid-life examination, corresponding to 0.40 (95% CI 0.39-0.41) kg/year for men and women. Both weight at age 20 years and weight at the mid-life examination were associated with mid-life blood pressures. On average, a 10 kg weight increase between age 20 years and mid-life was associated with 2.2 (95% CI 0.9-3.5) mmHg higher systolic and 1.7 (95% CI 0.9-2.5) mmHg higher diastolic mid-life blood pressure in men, and 3.2 (2.5-4.0) mmHg higher systolic and 2.4 (1.9-2.9) mmHg higher diastolic mid-life blood pressure in women. Mid-life weight was more closely associated than weight at age 20 years with mid-life blood pressure. For a given mid-life weight, blood pressure was higher in persons with higher weight gain from age 20 years.CONCLUSION: In sum, weight gain between early adulthood and mid-life was associated with higher mid-life blood pressure. The magnitude of the association indicates a potentially great public health impact of strategies to prevent weight gain throughout adulthood.
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