| 1. |
|
|
| 2. |
- Stray-Pedersen, Asbjorg, et al.
(författare)
-
Primary immunodeficiency diseases : Genomic approaches delineate heterogeneous Mendelian disorders
- 2017
-
Ingår i: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 139:1, s. 232-245
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Primary immunodeficiency diseases (PIDDs) are clinically and genetically heterogeneous disorders thus far associated with mutations in more than 300 genes. The clinical phenotypes derived from distinct genotypes can overlap. Genetic etiology can be a prognostic indicator of disease severity and can influence treatment decisions. Objective: We sought to investigate the ability of whole-exome screening methods to detect disease-causing variants in patients with PIDDs. Methods: Patients with PIDDs from 278 families from 22 countries were investigated by using whole-exome sequencing. Computational copy number variant (CNV) prediction pipelines and an exome-tiling chromosomal microarray were also applied to identify intragenic CNVs. Analytic approaches initially focused on 475 known or candidate PIDD genes but were nonexclusive and further tailored based on clinical data, family history, and immunophenotyping. Results: A likely molecular diagnosis was achieved in 110 (40%) unrelated probands. Clinical diagnosis was revised in about half (60/ 110) and management was directly altered in nearly a quarter (26/ 110) of families based on molecular findings. Twelve PIDD-causing CNVs were detected, including 7 smaller than 30 Kb that would not have been detected with conventional diagnostic CNV arrays. Conclusion: This high-throughput genomic approach enabled detection of disease-related variants in unexpected genes; permitted detection of low-grade constitutional, somatic, and revertant mosaicism; and provided evidence of a mutational burden in mixed PIDD immunophenotypes.
|
|
| 3. |
- Arteaga-Marrero, Natalia, et al.
(författare)
-
Radiation treatment monitoring using multimodal functional imaging: PET/CT ((18)F-Fluoromisonidazole & (18)F-Fluorocholine) and DCE-US.
- 2015
-
Ingår i: Journal of Translational Medicine. - : Springer Science and Business Media LLC. - 1479-5876. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- This study aims to assess the effect of radiation treatment on the tumour vasculature and its downstream effects on hypoxia and choline metabolism using a multimodal approach in the murine prostate tumour model CWR22. Functional parameters derived from Positron Emission Tomography (PET)/Computer Tomography (CT) with (18)F-Fluoromisonidazole ((18)F-FMISO) and (18)F-Fluorocholine ((18)F-FCH) as well as Dynamic Contrast-Enhanced Ultrasound (DCE-US) were employed to determine the relationship between metabolic parameters and microvascular parameters that reflect the tumour microenvironment. Immunohistochemical analysis was employed for validation.
|
|
| 4. |
- Arteaga-Marrero, Natalia, et al.
(författare)
-
Radiation treatment monitoring with DCE-US in CWR22 prostate tumor xenografts
- 2019
-
Ingår i: Acta Radiologica. - : Sage Publications. - 0284-1851 .- 1600-0455. ; 60:6, s. 788-797
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Longitudinal monitoring of potential radiotherapy treatment effects can be determined by dynamic contrast-enhanced ultrasound (DCE-US).Purpose: To assess functional parameters by means of DCE-US in a murine subcutaneous model of human prostate cancer, and their relationship to dose deposition and time-frame after treatment. A special focus has been placed to evaluate the vascular heterogeneity of the tumor and on the most suitable data analysis approach that reflects this heterogeneity.Material and Methods: In vivo DCE-US was acquired 24 h and 48 h after radiation treatment with a single dose of 7.5 Gy and 10 Gy, respectively. Tumor vasculature was characterized pixelwise using the Brix pharmacokinetic analysis of the time-intensity curves.Results: Longitudinal changes were detected (P < 0.001) at 24 h and 48 h after treatment. At 48 h, the eliminating rate constant of the contrast agent from the plasma, kel, was correlated (P ≤ 0.05) positively with microvessel density (MVD; rτ = 0.7) and negatively with necrosis (rτ = –0.6) for the treated group. Furthermore, Akep, a parameter related to transcapillary transport properties, was also correlated to MVD (rτ = 0.6, P ≤ 0.05).Conclusion: DCE-US has been shown to detect vascular changes at a very early stage after radiotherapy, which is a great advantage since DCE-US is non-invasive, available at most hospitals, and is low in cost compared to other techniques used in clinical practice.
|
|
| 5. |
- Bay-Richter, Cecilie, et al.
(författare)
-
A role for inflammatory metabolites as modulators of the glutamate N-methyl-D-aspartate receptor in depression and suicidality
- 2015
-
Ingår i: Brain, behavior, and immunity. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0889-1591 .- 1090-2139. ; 43, s. 110-117
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with depression and suicidality suffer from low-grade neuroinflammation. Proinflammatory cytokines activate indoleamine 2,3-dioxygenase, an initial enzyme of the kynurenine pathway. This pathway produces neuroactive metabolites, including quinolinic- and kynurenic acid, binding to the glutamate N-methyl-D-aspartate-receptor, which is hypothesized to be part of the neural mechanisms underlying symptoms of depression. We therefore hypothesized that symptoms of depression and suicidality would fluctuate over time in patients prone to suicidal behavior, depending on the degree of inflammation and kynurenine metabolite levels in the cerebrospinal fluid (CSF). Methods: We measured cytokines and kynurenine metabolites in CSF, collected from suicide attempters at repeated occasions over 2 years (total patient samples n = 143, individuals n = 30) and healthy controls (n = 36). The association between the markers and psychiatric symptoms was assessed using the Montgomery Asberg Depression Rating Scale and the Suicide Assessment Scale. Results: Quinolinic acid was increased and kynurenic acid decreased over time in suicidal patients versus healthy controls. Furthermore, we found a significant association between low kynurenic acid and severe depressive symptoms, as well as between high interleukin-6 levels and more severe suicidal symptoms. Conclusions: We demonstrate a long-term dysregulation of the kynurenine pathway in the central nervous system of suicide attempters. An increased load of inflammatory cytokines was coupled to more severe symptoms. We therefore suggest that patients with a dysregulated kynurenine pathway are vulnerable to develop depressive symptoms upon inflammatory conditions, as a result the excess production of the NMDA-receptor agonist quinolinic acid. This study provides a neurobiological framework supporting the use of NMDA-receptor antagonists in the treatment of suicidality and depression. (C) 2014 Elsevier Inc. All rights reserved.
|
|
| 6. |
- Freisling, Heinz, et al.
(författare)
-
Nut intake and 5-year changes in body weight and obesity risk in adults: results from the EPIC-PANACEA study
- 2018
-
Ingår i: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6207 .- 1436-6215. ; 57:7, s. 2399-2408
-
Tidskriftsartikel (refereegranskat)abstract
- © 2017 Springer-Verlag GmbH Germany Purpose: There is inconsistent evidence regarding the relationship between higher intake of nuts, being an energy-dense food, and weight gain. We investigated the relationship between nut intake and changes in weight over 5 years. Methods: This study includes 373,293 men and women, 25–70 years old, recruited between 1992 and 2000 from 10 European countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Habitual intake of nuts including peanuts, together defined as nut intake, was estimated from country-specific validated dietary questionnaires. Body weight was measured at recruitment and self-reported 5 years later. The association between nut intake and body weight change was estimated using multilevel mixed linear regression models with center/country as random effect and nut intake and relevant confounders as fixed effects. The relative risk (RR) of becoming overweight or obese after 5 years was investigated using multivariate Poisson regressions stratified according to baseline body mass index (BMI). Results: On average, study participants gained 2.1 kg (SD 5.0 kg) over 5 years. Compared to non-consumers, subjects in the highest quartile of nut intake had less weight gain over 5 years (−0.07 kg; 95% CI −0.12 to −0.02) (P trend = 0.025) and had 5% lower risk of becoming overweight (RR 0.95; 95% CI 0.92–0.98) or obese (RR 0.95; 95% CI 0.90–0.99) (both P trend < 0.008). Conclusions: Higher intake of nuts is associated with reduced weight gain and a lower risk of becoming overweight or obese.
|
|
| 7. |
- Glasø de Lange, Ann-Marie, et al.
(författare)
-
White matter integrity as a marker for cognitive plasticity in aging
- 2016
-
Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 47, s. 74-82
-
Tidskriftsartikel (refereegranskat)abstract
- Age-related differences in white matter (WM) integrity are substantial, but it is unknown whether between subject variability in WM integrity influences the capacity for cognitive improvement. We investigated the effects of memory training related to active and passive control conditions in older adults and tested whether WM integrity at baseline was predictive of training benefits. We hypothesized that (1) memory improvement would be restricted to the training group, (2) widespread areas would show greater mean diffusivity (MD) and lower fractional anisotropy in older adults relative to young adults, and (3) within these areas, variability in WM microstructure in the older group would be predictive of training gains. The results showed that only the group receiving training improved their memory. Significant age differences in MD and fractional anisotropy were found in widespread areas. Within these areas, voxelwise analyses showed a negative relationship between MD and memory improvement in 3 clusters, indicating that WM integrity could serve as a marker for the ability to adapt in response to cognitive challenges in aging.
|
|
| 8. |
- Real, Francisco Gomez, et al.
(författare)
-
Maternal age at delivery, lung function and asthma in offspring : a population-based survey
- 2018
-
Ingår i: European Respiratory Journal. - : EUROPEAN RESPIRATORY SOC JOURNALS LTD. - 0903-1936 .- 1399-3003. ; 51:6
-
Tidskriftsartikel (refereegranskat)abstract
- There is limited information about potential impact of maternal age on the respiratory health of offspring. We investigated the association of maternal age at delivery with adult offspring's lung function, respiratory symptoms and asthma, and potential differences according to offspring sex. 10 692 adults from 13 countries participating in the European Community Respiratory Health Survey (ECRHS) II responded to standardised interviews and provided lung function measurements and serum for IgE measurements at age 25-55 years. In logistic and linear multilevel mixed models we adjusted for participants' characteristics (age, education, centre, number of older siblings) and maternal characteristics (smoking in pregnancy, education) while investigating for differential effects by sex. Maternal age was validated in a subsample using data from the Norwegian birth registry. Increasing maternal age was associated with increasing forced expiratory volume in 1 s (2.33 mL per year, 95% CI 0.34-4.32 mL per year), more consistent in females (p(trend) 0.025) than in males (ptrend 0.14). Asthma (OR 0.85, 95% CI 0.79-0.92) and respiratory symptoms (OR 0.87, 95% CI 0.82-0.92) decreased with increasing maternal age (per 5 years) in females, but not in males (p(interaction) 0.05 and 0.001, respectively). The results were consistent across centres and not explained by confounding factors. Maternal ageing was related to higher adult lung function and less asthma/symptoms in females. Biological characteristics in offspring related to maternal ageing are plausible and need further investigation.
|
|
| 9. |
- St. Louis, Kenneth O., et al.
(författare)
-
Public attitudes toward stuttering in Europe : Within-country and between-country comparisons
- 2016
-
Ingår i: Journal of Communication Disorders. - : Elsevier BV. - 0021-9924. ; 62, s. 115-130
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Epidemiological research methods have been shown to be useful in determining factors that might predict commonly reported negative public attitudes toward stuttering. Previous research has suggested that stuttering attitudes of respondents from North America and Europe (i.e., "The West"), though characterized by stereotypes and potential stigma, are more positive than those from several other regions of the world. This inference assumes that public attitudes within various regions characterized by "The West" are similar. Purpose: This study aimed to determine the extent to which public stuttering attitudes are similar or different both within regions of three different European countries and between or among five different European countries or similar geographic areas. It also aimed to compare these European attitudes to attitudes from 135 samples around the world using a standard measure. Material and methods: Using convenience sampling, 1111 adult respondents from eight different investigations completed the Public Opinion Survey of Human Attributes-Stuttering (POSHA-S) in the dominant language of each country or area. In Study I, the authors compared attitudes within three different regions of Bosnia & Herzegovina, Italy, and Norway. In Study II, the authors compared attitudes between combined samples from Bosnia & Herzegovina, Italy, and Norway (with additional respondents from Sweden), and two other samples, one from Germany and the other from Ireland and England. Results: Attitudes of adults from the three samples within Bosnia & Herzegovina, Italy, and Norway were remarkably similar. By contrast, attitudes between the five different countries or area were quite dramatically different. Demographic variables on the POSHA-S did not predict the rank order of these between-country/area differences. Compared to the POSHA-S worldwide database, European attitudes ranged from less positive than average (i.e., Italians) to more positive than average (i.e., Norwegians and Swedes). Conclusion: Factors related to national identity appear to play a significant role in differences in public attitudes in Europe and should be explored in future research.
|
|
| 10. |
- Turesson, Ingemar, et al.
(författare)
-
Rapidly changing myeloma epidemiology in the general population: Increased incidence, older patients, and longer survival
- 2018
-
Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 101:2, s. 237-244
-
Tidskriftsartikel (refereegranskat)abstract
- The incidence of multiple myeloma is characterized by a steep increase with advancing age. Dramatic improvements in survival have been reported in clinical trials; however, elderly patients are generally underrepresented in these. The aims of this study are to review patterns of incidence and survival in multiple myeloma in the general population. We searched PubMed for population-based studies on trends in incidence and survival published between January 1, 2000 and June 30, 2017 and based on regional or national cancer registries and report the following results of the review. The age-adjusted incidence of multiple myeloma has increased during the second half of the twentieth century in some countries but remained stable in areas with high case ascertainment and access to universal medical care. The crude incidence is increasing globally due to an aging population. Survival rates have improved, and 5-year relative survival rates are now around 50% and over 60% in patients 65-70years or younger. Preliminary data suggest a 3-fold increase in the prevalence of multiple myeloma. We conclude that the number of multiple myeloma patients is increasing in the general population due to (i) aging populations and (ii) more patients living longer due to modern drugs.
|
|
