| 1. |
- Bergström, Petra, et al.
(författare)
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Herpes Simplex Virus 1 and 2 Infections during Differentiation of Human Cortical Neurons
- 2021
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Ingår i: Viruses-Basel. - : MDPI AG. - 1999-4915. ; 13:10
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Tidskriftsartikel (refereegranskat)abstract
- Herpes simplex virus 1 (HSV-1) and 2 (HSV-2) can infect the central nervous system (CNS) with dire consequences; in children and adults, HSV-1 may cause focal encephalitis, while HSV-2 causes meningitis. In neonates, both viruses can cause severe, disseminated CNS infections with high mortality rates. Here, we differentiated human induced pluripotent stem cells (iPSCs) towards cortical neurons for infection with clinical CNS strains of HSV-1 or HSV-2. Progenies from both viruses were produced at equal quantities in iPSCs, neuroprogenitors and cortical neurons. HSV-1 and HSV-2 decreased viability of neuroprogenitors by 36.0% and 57.6% (p < 0.0001), respectively, 48 h post-infection, while cortical neurons were resilient to infection by both viruses. However, in these functional neurons, both HSV-1 and HSV-2 decreased gene expression of two markers of synaptic activity, CAMK2B and ARC, and affected synaptic activity negatively in multielectrode array experiments. However, unaltered secretion levels of the neurodegeneration markers tau and NfL suggested intact axonal integrity. Viral replication of both viruses was found after six days, coinciding with 6-fold and 22-fold increase in gene expression of cellular RNA polymerase II by HSV-1 and HSV-2, respectively. Our results suggest a resilience of human cortical neurons relative to the replication of HSV-1 and HSV-2.
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| 2. |
- Wang, Gang, et al.
(författare)
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Assessment of chronic bronchitis and risk factors in young adults : results from BAMSE
- 2020
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Ingår i: European Respiratory Journal. - Stockholm : Karolinska Institutet, Dept of Clinical Science and Education, Södersjukhuset. - 0903-1936 .- 1399-3003.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Chronic bronchitis is associated with substantial morbidity among elderly adults, but little is known about its prevalence and risk factors in young adults. Our aim was to assess the prevalence and early life risk factors for chronic bronchitis in young adults. METHODS: Questionnaire data and clinical measures from the 24-year follow-up of the Swedish BAMSE cohort were used. We assessed chronic bronchitis (CB) as the combination of cough and mucus production in the morning during winter. Environmental and clinical data from birth and onwards were used for analyses of risk factors. RESULTS: At the 24-year follow-up, 75% (n=3064) participants completed the questionnaire and 2030 performed spirometry. The overall prevalence of CB was 5.5% (n=158) with similar estimates in males and females. Forty-nine percent of CB cases experienced more than 3 self-reported respiratory infections in the last year compared to 18% in non-CB subjects (p<0.001), and 37% of cases were current smokers (versus 19%). Statistically significant lower post-FEV(1)/FVC were observed in CB compared to non-CB subjects (mean z-score -0.06 versus 0.13, p=0.027). Daily smoking (adjusted Odds Ratio, aOR=3.85, p<0.001), air pollution exposure (black carbon during ages 1-4 years old, aOR=1.71 per 1 μg·m(3) increase, p=0.009) and exclusive breast-feeding during four months or more (aOR=0.66, p=0.044) were associated with CB. CONCLUSION: Chronic bronchitis in young adults is associated with recurrent respiratory infections. Besides smoking, our results support role of early life exposures, such as air pollution and exclusive breast-feeding, for respiratory health later in life.
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| 3. |
- Wang, Gang, et al.
(författare)
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Early-life risk factors for reversible and irreversible airflow limitation in young adults : findings from the BAMSE birth cohort
- 2021
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Ingår i: Thorax. - : BMJ Publishing Group Ltd. - 0040-6376 .- 1468-3296. ; 76:5, s. 503-507
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to determine prevalence and early-life risk factors for reversible and irreversible airflow limitation in young adults from the general population. Among young adults in their 20s, the prevalence was 5.3% for reversible airflow limitation and 2.0% for irreversible airflow limitation. While parental asthma was the only risk factor for development of reversible airflow limitation, the risk factors for development of irreversible airflow limitation were current asthma, childhood respiratory tract infections and asthma, and exposure to air pollution.
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| 4. |
- Agholme, Lotta, et al.
(författare)
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Low-dose γ-secretase inhibition increases secretion of Aβ peptides and intracellular oligomeric Aβ.
- 2017
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Ingår i: Molecular and cellular neurosciences. - : Elsevier BV. - 1095-9327 .- 1044-7431. ; 85, s. 211-219
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Tidskriftsartikel (refereegranskat)abstract
- γ-Secretase inhibitors have been considered promising drug candidates against Alzheimer's disease (AD) due to their ability to reduce amyloid-β (Aβ) production. However, clinical trials have been halted due to lack of clinical efficacy and/or side effects. Recent in vitro studies suggest that low doses of γ-secretase inhibitors may instead increase Aβ production. Using a stem cell-derived human model of cortical neurons and low doses of the γ-secretase inhibitor DAPT, the effects on a variety of Aβ peptides were studied using mass spectrometry. One major focus was to develop a novel method for specific detection of oligomeric Aβ (oAβ), and this was used to study the effects of low-dose γ-secretase inhibitor treatment on intracellular oAβ accumulation. Low-dose treatment (2 and 20nM) with DAPT increased the secretion of several Aβ peptides, especially Aβx-42. Furthermore, using the novel method for oAβ detection, we found that 2nM DAPT treatment of cortical neurons resulted in increased oAβ accumulation. Thus, low dose-treatment with DAPT causes both increased production of long, aggregation-prone Aβ peptides and accumulation of intracellular Aβ oligomers, both believed to contribute to AD pathology.
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| 5. |
- Bergström, Helena, 1971-, et al.
(författare)
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"Jag är inte diktator, jag är också mamma" : om föräldrastöd och föräldraansvar kring barns fetma och övervikt
- 2012
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Ingår i: Barn. - Trondheim : NAVF's Senter for Barneforskning. - 0800-1669 .- 2535-5449. ; 30:4, s. 41-57
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Tidskriftsartikel (refereegranskat)abstract
- I Sverige liksom i många andra länder har barns övervikt och fetma ökat. Ett sätt att motverka denna problematik är stöd riktat till föräldrar. Föräldrar anses ha en central betydelse för barns matvanor och fysiska aktivitet och stöd och råd till föräldrar poängterar gränssättning, uppmuntran och att föräldern ska fungera som en förebild för barnet. Genom intervjuer med föräldrar till barn med övervikt/fetma visar denna artikel hur föräldrar hanterar råd och anvisningar i sitt dagliga liv. Det visar sig att föräldrarna står inför ett komplext dilemma som innebär att de beaktar såväl fysisk som psykisk hälsa samt den vardagliga förhandlingen mellan föräldrar och barn. Sett ur ett omsorgsetiskt perspektiv utmanas idén om en rationell förälder som handlar i enlighet med kunskaper om vad som är en hälsosam livsstil. Föräldraskap innebär mycket mer än att kontrollera barnets vikt och sätta gränser.
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| 6. |
- Bergström, Petra, et al.
(författare)
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Amyloid precursor protein expression and processing are differentially regulated during cortical neuron differentiation
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid precursor protein (APP) and its cleavage product amyloid beta (A beta) have been thoroughly studied in Alzheimer's disease. However, APP also appears to be important for neuronal development. Differentiation of induced pluripotent stem cells (iPSCs) towards cortical neurons enables in vitro mechanistic studies on human neuronal development. Here, we investigated expression and proteolytic processing of APP during differentiation of human iPSCs towards cortical neurons over a 100-day period. APP expression remained stable during neuronal differentiation, whereas APP processing changed. alpha-Cleaved soluble APP (sAPP alpha) was secreted early during differentiation, from neuronal progenitors, while beta-cleaved soluble APP (sAPP beta) was first secreted after deep-layer neurons had formed. Short A beta peptides, including A beta 1-15/16, peaked during the progenitor stage, while processing shifted towards longer peptides, such as A beta 1-40/42, when post-mitotic neurons appeared. This indicates that APP processing is regulated throughout differentiation of cortical neurons and that amyloidogenic APP processing, as reflected by A beta 1-40/42, is associated with mature neuronal phenotypes.
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| 7. |
- Bergström, Petra, et al.
(författare)
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Association of NFE2L2 and KEAP1 haplotypes with amyotrophic lateral sclerosis.
- 2014
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Ingår i: Amyotrophic lateral sclerosis & frontotemporal degeneration. - : Informa UK Limited. - 2167-9223 .- 2167-8421. ; 15:1-2, s. 130-137
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron syndrome influenced by oxidative stress. The transcription factor Nrf2 and its repressor Keap1 constitute an important defence system in cellular protection against oxidative stress. Here we hypothesize that common genetic variations in the genes NFE2L2 and KEAP1, encoding Nrf2 and Keap1, may influence the risk and phenotype of ALS. Five hundred and twenty-two Swedish patients with sporadic ALS (SALS) and 564 Swedish control subjects were studied. Eight tag SNPs in NFE2L2 and three tag SNPs in KEAP1 were genotyped by allelic discrimination and three functional NFE2L2 promoter SNPs were genotyped by sequencing. One NFE2L2 haplotype (GGGAC) was associated with decreased risk of SALS (OR = 0.62 per allele, p = 0.003) and one haplotype in KEAP1 (CGG) was associated with later SALS onset (+3.4 years per allele, p = 0.015). When stratified by subgroup, one haplotype in NFE2L2, GAGCAGA including three functional promoter SNPs associated with high Nrf2 protein expression, was associated with 4.0 years later disease onset per allele in subgroup ALS (p = 0.008). In conclusion, these results suggest that variations in NFE2L2 and KEAP1, encoding two central proteins in cellular oxidative stress defence, may influence SALS pathogenesis.
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| 8. |
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| 9. |
- Berntsson, Matilda, 1968, et al.
(författare)
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Viral and bacterial aetiologies of male urethritis: findings of a high prevalence of Epstein-Barr virus
- 2010
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Ingår i: International Journal of STD & AIDS. - 0956-4624. ; 21:3, s. 191-194
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Tidskriftsartikel (refereegranskat)abstract
- Male urethritis is one of the most common sexually transmitted infections (STIs). However, the aetiology is still unclear in many cases. In this study the prevalences of Epstein-Barr virus (EBV), herpes simplex virus type 1 (HSV-1), HSV-2, cytomegalovirus (CMV), adenovirus, Chlamydia trachomatis, Mycoplasma genitalium and Ureaplasma urealyticum (including subtyping) were investigated. Samples from 112 male STI attendants with microscopically verified urethritis and from a control group of 103 men without clinical or microscopic signs of urethritis were analysed. Prevalences in the urethritis group compared with the controls were as follows: EBV 21%, 6% (P < 0.01); C. trachomatis 15%, 3% (P < 0.01); M. genitalium 6%, 1% (P = 0.067) and U. urealyticum 10%, 10% (ns). The results for HSV-1, HSV-2, CMV and adenovirus were negative in patients, and therefore not analysed in the controls. EBV was shown to be an independent predictor of urethritis and may play a role in its pathogenesis.
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| 10. |
- Blom, Victoria, 1975-, et al.
(författare)
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Stress in paid and unpaid work as related to cortisol and subjective health complaints in women working in the public health care sector
- 2017
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Ingår i: International Journal of Workplace Health Management. - 1753-8351 .- 1753-836X. ; 10:4, s. 286-299
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Focusing on 420 women employed within the woman-dominated health care sector, the purpose of this paper is to investigate how any variation in their total workload (TWL) in terms of paid and unpaid work relate to various subjective health complaints (SHC) (n=420) and the neuroendocrine stress marker cortisol (n=68).Design/methodology/approach: The authors explored how any variation in their TWL in terms of paid and unpaid work related cross-sectionally to SHC (n=420), and the neuroendocrine stress marker cortisol (n=68).Findings: Hierarchical regression analyses showed that stress of unpaid work was most strongly related to diurnal variations in cortisol. Both stress of paid and unpaid work as well as TWL stress, but not hours spent on TWL, were related to SHC.Practical implications: Taken together, objective measures of hours spent on various TWL domains were unrelated to outcome measures while perceptions of having too much TWL and TWL stress were linked to both cortisol and SHC, i.e. how individuals perceive a situation seem to be more important for health than the actual situation, which has implications for research and efforts to reduce individual TWL.Originality/value: This study is unique in showing that unpaid work and perceptions having too much TWL relate to stress markers in women working in the public health care sector.
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