| 1. |
- Kononenko, Olga, et al.
(författare)
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Intra- and interregional coregulation of opioid genes : broken symmetry in spinal circuits
- 2017
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Ingår i: The FASEB Journal. - : John Wiley & Sons. - 0892-6638 .- 1530-6860. ; 31:5, s. 1953-1963
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Tidskriftsartikel (refereegranskat)abstract
- Regulation of the formation and rewiring of neural circuits by neuropeptides may require coordinated production of these signaling molecules and their receptors that may be established at the transcriptional level. Here, we address this hypothesis by comparing absolute expression levels of opioid peptides with their receptors, the largest neuropeptide family, and by characterizing coexpression (transcriptionally coordinated) patterns of these genes. We demonstrated that expression patterns of opioid genes highly correlate within and across functionally and anatomically different areas. Opioid peptide genes, compared with their receptor genes, are transcribed at much greater absolute levels, which suggests formation of a neuropeptide cloud that covers the receptor-expressed circuits. Surprisingly, we found that both expression levels and the proportion of opioid receptors are strongly lateralized in the spinal cord, interregional coexpression patterns are side specific, and intraregional coexpression profiles are affected differently by left-and right-side unilateral body injury. We propose that opioid genes are regulated as interconnected components of the same molecular system distributed between distinct anatomic regions. The striking feature of this system is its asymmetric coexpression patterns, which suggest side-specific regulation of selective neural circuits by opioid neurohormones.
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| 2. |
- Blöndal, Viiu, et al.
(författare)
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Allergic sensitisation and type-2 inflammation is associated with new-onset and persistent allergic disease
- 2023
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Ingår i: Clinical and Translational Allergy. - : Wiley-Blackwell. - 2045-7022. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Allergic disease is common. The aim of this study was to look at the change in asthma and rhinitis over time and to characterise factors contributing to remission and persistence of disease.Methods: This cohort study included 255 individuals with or without asthma and or rhinitis that participated in a population survey and a follow-up 10 years later. The participants were tested for allergic sensitisation, total IgE, multiplex allergen component analysis and type-2 inflammatory markers: exhaled nitric oxide (FENO), eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN).Results: Of the 132 healthy individuals, 112 remained healthy, 16 developed rhinitis, 4 asthma and rhinitis over the 10 years. Out of 82 subjects with rhinitis, 26 went into remission, 53 remained unchanged and 3 developed asthma in addition to rhinitis. None of the 41 participants with asthma and rhinitis went into remission. Subjects with persistent rhinitis and asthma had higher levels of total IgE (odds ratio [OR] 95% confidence interval [CI]: 6.16 [3.05-12.5]) at baseline and after 10 years, and FENO and ECP at baseline (OR per log unit increase, 95% CI 5.21 [1.20-22.7] and 6.32 [1.52-26.4], respectively), compared with those that remained healthy. Subjects with persistent rhinitis were more likely to be sensitised to grass pollen and had higher total IgE levels than those that went into remission. Individuals with persistent asthma were more likely to be sensitised to tree pollen and furry animals than those with only persistent rhinitis (OR 95% CI: 3.50 [1.29-9.49] and 6.73 [2.00-22.6], respectively).Conclusion: IgE sensitisation and total IgE levels are associated with the persistence of rhinitis and asthma. Participants with persistent allergic disease had higher levels of allergen sensitisation and type 2 inflammation markers at baseline than those who remained healthy.
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| 3. |
- Gagatek, Sebastian, et al.
(författare)
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Validation of Clinical COPD Phenotypes for Prognosis of Long-Term Mortality in Swedish and Dutch Cohorts
- 2022
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Ingår i: COPD. - : Informa Healthcare. - 1541-2555 .- 1541-2563. ; 19:1, s. 330-338
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Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with variable mortality risk. The aim of our investigation was to validate a simple clinical algorithm for long-term mortality previously proposed by Burgel et al. in 2017. Subjects with COPD from two cohorts, the Swedish PRAXIS study (n = 784, mean age (standard deviation (SD)) 64.0 years (7.5), 42% males) and the Rotterdam Study (n = 735, mean age (SD) 72 years (9.2), 57% males), were included. Five clinical clusters were derived from baseline data on age, body mass index, dyspnoea grade, pulmonary function and comorbidity (cardiovascular disease/diabetes). Cox models were used to study associations with 9-year mortality. The distribution of clinical clusters (1-5) was 29%/45%/8%/6%/12% in the PRAXIS study and 23%/26%/36%/0%/15% in the Rotterdam Study. The cumulative proportion of deaths at the 9-year follow-up was highest in clusters 1 (65%) and 4 (72%), and lowest in cluster 5 (10%) in the PRAXIS study. In the Rotterdam Study, cluster 1 (44%) had the highest cumulative mortality and cluster 5 (5%) the lowest. Compared with cluster 5, the meta-analysed age- and sex-adjusted hazard ratio (95% confidence interval) for cluster 1 was 6.37 (3.94-10.32) and those for clusters 2 and 3 were 2.61 (1.58-4.32) and 3.06 (1.82-5.13), respectively. Burgel's clinical clusters can be used to predict long-term mortality risk. Clusters 1 and 4 are associated with the poorest prognosis, cluster 5 with the best prognosis and clusters 2 and 3 with intermediate prognosis in two independent cohorts from Sweden and the Netherlands.
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| 4. |
- Islam, Md. Tauhidul, et al.
(författare)
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Life-course trajectories of body mass index and subsequent cardiovascular risk among Chinese population
- 2019
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Examining body mass index (BMI) change over life course is crucial for cardiovascular health promotion and prevention. So far, there is very few evidence on the long-term change of BMI from childhood to late life. This study aimed to examine the life-course trajectory patterns of BMI and then to link the trajectory patterns to cardiovascular risk factors in adulthood.Methods: Based on longitudinal data from the China Health and Nutrition Survey, 5276 participants (aged 6-60) at baseline (in 1989) with up to 7 measurements of BMI during 1989-2009 were selected in this study. Cardiovascular risk factors including high blood pressure, high blood glucose and high blood lipids were assessed in 2411 participants in 2009. Latent growth curve modelling was used to analyse the BMI trajectories, and logistic regression was used to examine the associations between trajectory patterns and cardiovascular risk factors.Results: Four trajectories patterns of BMI over life course (age 6-80) were identified: Normal-Stable (22.4% of the total participants), Low normal-Normal-Stable (44.1%), Low normal-NormalOverweight (27.2%), and Overweight-Obese (4.3%). Compared to those with Normal-Stable pattern, those with Low normal-Normal-Stable pattern, Low normal-Normal-Overweight pattern and Overweight-Obese pattern had higher risk of high blood pressure (odds ratio range = 1.6-6.6), high blood glucose (1.7-9.1), dyslipidemia (2.6-5.9) and having at least two of the three cardiovascular risk factors (3.9-30.9).Conclusions: Having a stable BMI within normal range over life course is associated with the lowest cardiovascular risk, whereas remaining overweight and obese over life course is associated with the highest cardiovascular risk.
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| 5. |
- Kisiel, Marta A., 1984-, et al.
(författare)
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Clustering Analysis Identified Three Long COVID Phenotypes and Their Association with General Health Status and Working Ability
- 2023
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 12:11
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Tidskriftsartikel (refereegranskat)abstract
- Background/aim: This study aimed to distinguish different phenotypes of long COVID through the post-COVID syndrome (PCS) score based on long-term persistent symptoms following COVID-19 and evaluate whether these symptoms affect general health and work ability. In addition, the study identified predictors for severe long COVID.Method: This cluster analysis included cross-sectional data from three cohorts of patients after COVID-19: non-hospitalized (n = 401), hospitalized (n = 98) and those enrolled at the post-COVID outpatient's clinic (n = 85). All the subjects responded to the survey on persistent long-term symptoms and sociodemographic and clinical factors. K-Means cluster analysis and ordinal logistic regression were used to create PCS scores that were used to distinguish patients' phenotypes.Results: 506 patients with complete data on persistent symptoms were divided into three distinct phenotypes: none/mild (59%), moderate (22%) and severe (19%). The patients with severe phenotype, with the predominating symptoms were fatigue, cognitive impairment and depression, had the most reduced general health status and work ability. Smoking, snuff, body mass index (BMI), diabetes, chronic pain and symptom severity at COVID-19 onset were factors predicting severe phenotype.Conclusion: This study suggested three phenotypes of long COVID, where the most severe was associated with the highest impact on general health status and working ability. This knowledge on long COVID phenotypes could be used by clinicians to support their medical decisions regarding prioritizing and more detailed follow-up of some patient groups.
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| 6. |
- Kisiel, Marta, 1984-, et al.
(författare)
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Data-driven questionnaire-based cluster analysis of asthma in Swedish adults
- 2020
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Ingår i: npj Primary Care Respiratory Medicine. - : Nature Research. - 2055-1010. ; 30:1
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to identify asthma phenotypes through cluster analysis. Cluster analysis was performed using self-reported characteristics from a cohort of 1291 Swedish asthma patients. Disease burden was measured using the Asthma Control Test (ACT), the mini Asthma Quality of Life Questionnaire (mini-AQLQ), exacerbation frequency and asthma severity. Validation was performed in 748 individuals from the same geographical region. Three clusters; early onset predominantly female, adult onset predominantly female and adult onset predominantly male, were identified. Early onset predominantly female asthma had a higher burden of disease, the highest exacerbation frequency and use of inhaled corticosteroids. Adult onset predominantly male asthma had the highest mean score of ACT and mini-AQLQ, the lowest exacerbation frequency and higher proportion of subjects with mild asthma. These clusters, based on information from clinical questionnaire data, might be useful in primary care settings where the access to spirometry and biomarkers is limited.
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| 7. |
- Kisiel, Marta, 1984-, et al.
(författare)
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Medical students experience mistreatment, with a focus on gender discrimination. Cross-sectional study at one Swedish medical school
- 2023
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Ingår i: Cogent Social Sciences. - : Taylor & Francis. - 2331-1886. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to study discrimination, with a focus on gender and sexual harassment among medical students at Uppsala University in Sweden. A survey was sent via email to all registered medical students in the spring semester of 2020. Data were compared with two previous studies. Questions about gender and sexual harassment were the same as in the study conducted in 2002 and 2013. In addition, the 2020 survey included a question about other grounds of discrimination. Forty percent, that is, 453 out of 1,130 medical students, participated. The proportion of students reporting gender-based discrimination during the preclinical semesters was similar for females and males. During the clinical semesters, significantly more females than males reported gender discrimination (41% vs. 21.5%, p = 0.005) and sexual harassment (22% vs. 5%, p = 0.001). Physicians were the most commonly reported perpetrator. Reports about not being respected had increased from 2% to 20% between 2013 and 2020 among female clinical students. The prevalence of those who experienced several sexually harassing behaviors increased for the female and male clinical students and the female preclinical students. Receiving an unwelcome touch increased from 1% to 7% for the female clinical students. Discrimination due to ethnicity was reported by 36% of the students born in a country other than Sweden compared to 3% of those born in Sweden. Our findings confirm that experiences of different forms of discrimination exist in this medical school, and females and minorities are particularly affected.
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| 8. |
- Kisiel, Marta, 1984-, et al.
(författare)
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The risk of respiratory tract infections and antibiotic use in a general population and among people with asthma
- 2021
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Ingår i: ERJ Open Research. - : European Respiratory Society (ERS). - 2312-0541. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- Aim The aim of this study was to investigate occupational, environmental, early life and other risk factors associated with respiratory infections and antibiotics use in a general population and among asthmatic individuals. Method This study included 15842 participants of the Respiratory Health in Northern Europe (RHINE) study aged 25–54 years from five Nordic countries, who answered a questionnaire covering respiratory outcomes, exposures, demographic characteristics and numbers of infections and courses of antibiotics in the last 12 months. Multiple logistic regression with and without adjustment for age, sex, smoking status, body mass index and centre were used to study the risk of infection and antibiotics in relation to asthma, and also the association between infection and antibiotics and occupations. Results In the whole population, 11.6% reported having three or more respiratory infections, and 14.7% had used antibiotics because of respiratory tract infections within the last year. Asthmatic participants reported tripled odds for such infections (adjusted OR 2.98, 95% CI 2.53–3.52) and antibiotics use (adjusted OR 3.67, 95% CI 3.18–4.24) as compared to non-asthmatic participants. Both in the general and the asthmatic population, female sex, obesity and exposure to building dampness were associated with respiratory infections. Female sex and current smoking and living in Tartu were associated with antibiotic use. The use of antibiotics was doubled in people hospitalised for severe respiratory infection in childhood. Conclusion In this study we identified several factors associated with increased respiratory infections and use of antibiotics in a general population and among asthmatic individuals. The frequency of respiratory infections and subsequent antibiotic treatment were increased among those with asthma. © The authors 2021.
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| 9. |
- Kreiberg, David, et al.
(författare)
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A Faster Procedure for Estimating SEMs Applying Minimum Distance Estimators With a Fixed Weight Matrix
- 2023
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Ingår i: Structural Equation Modeling. - : Taylor & Francis Group. - 1070-5511 .- 1532-8007. ; 30:2, s. 214-221
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Tidskriftsartikel (refereegranskat)abstract
- This study presents a separable nonlinear least squares (SNLLS) implementation of the minimum distance (MD) estimator employing a fixed-weight matrix for estimating structural equation models (SEMs). In contrast to the standard implementation of the MD estimator, in which the complete set of parameters is estimated using nonlinear optimization, the SNLLS implementation allows a subset of parameters to be estimated using (linear) least squares (LS). The SNLLS implementation possesses a number of benefits, such as faster convergence, better performance in ill-conditioned estimation problems, and fewer required starting values. The present work demonstrates that SNLLS, when applied to SEM estimation problems, significantly reduces the estimation time. Reduced estimation time makes SNLLS particularly useful in applications involving some form of resampling, such as simulation and bootstrapping.
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| 10. |
- Liu, Wen, et al.
(författare)
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Colorectal cancer risk susceptibility loci in a Swedish population
- 2022
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Ingår i: Molecular Carcinogenesis. - : Wiley. - 0899-1987 .- 1098-2744. ; 61:3, s. 288-300
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Tidskriftsartikel (refereegranskat)abstract
- To search for colorectal cancer (CRC) risk loci, Swedish samples were used for a genome-wide haplotype analysis. A logistic regression model was employed in 2663 CRC cases and 1642 controls in the discovery analysis. Three analyses were done, on all, familial-, and nonfamilial CRC samples and only results with odds ratio (OR) > 1 were analyzed. single nucleotide polymorphism (SNP) analysis did not generate any statistically significant results. Haplotype analysis suggested novel loci, on chromosome 2q36.1 (OR = 1.71, p value = 5.6924 × 10-8 ) in all CRC samples, chromosome 1q43 (OR = 4.04 p value = 3.24 × 10-8 ) in familial CRC samples, and two hits in nonfamilial CRC samples, chromosomes 2q36.1 (OR = 1.71 p value = 5.69 × 10-8 ) and 3p24.3 (OR = 1.62 p value = 6.21 × 10-9 ). Moreover, one locus on chromosome 20q13.33 was suggested in analyses of all samples, and five more novel loci were suggested on chromosomes 10q25.3, 15q,22.31, 17p11.2, 1p34.2, and 3q24. The haplotypes from the analysis of all samples were replicated in a second study of CRC cases and controls from the same part of Sweden. In summary, using haplotype analysis in Swedish CRC samples, the best hits were novel loci and the locus on chromosomes 2q36.1 and 20q13.33 suggested in the analysis of all samples were confirmed in a second cohort. The ORs were often higher than ORs from published genome-wide association study (GWAS). The study suggested it was possible that a risk locus could involve more than one gene, and that haplotypes could give information on the gene or genes possibly involved in the risk at specific locus.
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