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- Löfdahl, Magnus J, et al.
(author)
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Increased intraepithelial T-cells in stable COPD
- 2008
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In: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 102:12, s. 1812-1818
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Journal article (peer-reviewed)abstract
- BACKGROUND: The airway epithelium is the first line of defence in the response to inhaled particles and irritants. Chronic obstructive pulmonary disease (COPD) is an inflammatory disease characterised by an irreversible loss of lung function, with cigarette smoking as a major risk factor. Here, we address intraepithelial T-cells in COPD, as these cells are a distinct T-cell subtype thought to have important regulatory functions. We hypothesised that intraepithelial T-cells play a role in the response to lung irritants and that the T-cell populations would be altered and associated with signs of inflammation in COPD. METHODS: Bronchoscopy with endobronchial mucosal biopsy sampling was performed in 22 patients (mean age; 57) with stable COPD (median FEV(1)% predicted: 51). Age- and smoking- matched smokers (S) with normal lung function (n=14) and age-matched non-smokers (NS) (n=15) served as controls. Airway inflammation was recorded visually using bronchitis index (BI). Biopsy specimens were processed into glycol methacrylate resin and inflammatory cells were stained immunohistochemically. RESULTS: The number of intraepithelial CD4+ T-cells were significantly higher in COPD patients compared to smokers as well as trend towards significance in non-smokers (p=0.005 and p=0.036, respectively), whereas intraepithelial CD8+ T-cells number were increased in patients with COPD compared to non-smokers (p=0.017). Both patients with COPD and smokers had a higher BI than non-smokers (p<0.001 for both). CONCLUSIONS: The present data suggest a role for intraepithelial CD4+ and CD8+ T-cells in stable COPD and indicate that T-cells are of importance in the long-term inflammatory response in COPD or, alternatively, play a regulatory role.
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- Al-Shamkhi, Nasrin, et al.
(author)
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Important non-disease-related determinants of exhaled nitric oxide levels in mild asthma – results from the Swedish GA2LEN study
- 2016
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In: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 46:9, s. 1185-1193
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Journal article (peer-reviewed)abstract
- Background: Fractional exhaled nitric oxide (FeNO) has a potential clinical role in asthma management. Constitutive factors such as age, height and gender, as well as individual characteristics, such as IgE sensitization and smoking, affect the levels of FeNO in population-based studies. However, their effect on FeNO in subjects with asthma has been scarcely studied. Objective: To study the effects on FeNO of these commonly regarded determinants, as demonstrated in healthy subjects, as well as menarche age and parental smoking, in a population of asthmatics. Material and Methods: Fractional exhaled nitric oxide was measured in 557 subjects with asthma from the Swedish GA2LEN study. Allergic sensitization was assessed by skin prick tests to most common aeroallergens. Upper airway comorbidities, smoking habits, smoking exposure during childhood and hormonal status (for women) were questionnaire-assessed. Results: Male gender (P < 0.001), greater height (P < 0.001) and sensitization to both perennial allergens and pollen (P < 0.001) are related to higher FeNO levels. Current smoking (P < 0.001) and having both parents smoking during childhood, vs. having neither (P < 0.001) or only one parent smoking (P = 0.002), are related to lower FeNO. Women with menarche between 9 and 11 years of age had lower FeNO than those with menarche between 12 and 14 years of age (P = 0.03) or 15 and 17 years of age (P = 0.003). Conclusions and Clinical relevance: Interpreting FeNO levels in clinical practice is complex, and constitutional determinants, as well as smoking and IgE sensitisation, are of importance in asthmatic subjects and should be accounted for when interpreting FeNO levels. Furthermore, menarche age and parental smoking during childhood and their effects on lowering FeNO deserve further studies. © 2016 John Wiley & Sons Ltd
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- Asplund, Erik, et al.
(author)
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Framsyn för Norrbotten och Västerbotten : en idéskrift om utvecklingsinsatser idag och imorgon
- 2009
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Reports (other academic/artistic)abstract
- Rapport från DARE delprojekt regional framsyn. Etapp 1; scenarier och förslag på aktiviteter.Detta dokument är slutrapporten från den regionala framsynsprocessen som drevs 2008-2009 inom projektet DARE – Development Arena for Research and Entrepreneurship.Framsynen har verkat efter ett normativt och handlingsinriktat angreppssätt. Ledmotiv för processen har varit frågor som: Hur vill vi ha det? Varför är det inte så nu? Vad behöver vi göra nu och i framtiden? Regionen kan sägas kännetecknas av att den är rik på naturresurser och fattig på folk. Det är bakgrunden till de fokusområden som framsynen behandlat- Grönare näringsliv (hur kan nya och miljöeffektivare produkter och tjänsterutvecklas effektivare?)- Demografiutveckling (hur kan samhällsfunktionerna bestå med inverteradebefolkningspyramider och hur kan utvecklingen mot en åldrande befolkningvändas?)Lite tvärs över båda frågorna ovan hamnar ett annat fokus; regionens attraktivitet. Inom detta område har en ung framsyn genomförts med deltagare från olika delar av Norrbotten.Framsynen har gått steg för steg genom visioner, analys av framgångsfaktorer, scenarieskapande, förslag på åtgärder och prioritering av dessa. Under genomförandet har det uppstått ett antal avknoppningar i form av t ex nya samarbeten och projekt. Ett av de sistnämnda var den unga framsynen som genomfördes med finansiering av Norrbottens läns landsting.Bland de prioriterade förslagen som redovisas i denna rapport dominerar olika aktiviteter för att knyta samman olika aktörer och grupper inom regionen och på så sätt göra mer av mindre. Många av förslagen visar regionala aktörers förväntningar på universitetens roll i den regionala utvecklingen och markerar ett intresse av tätare samverkan meduniversiteten. Förslagen berör alla verksamheter inom universiteten, såväl utbildning, forskning och förvaltning. Bland de prioriterade förslagen finns:• Stimulera gröna affärs och teknikutvecklingsallianser för regionens småföretag• Stimulera ”den lille forskaren” – en modell för småföretagens forskarkollektiv• Utred grönare näringsliv som gemensamt profilområde för regionens universitet• Stärk företagsnyttig forskning & utvecklingsinsatser kring ”age management”• Etablera ett ”integrationsnätverk” för universitetens studenter & det regionalasamhället• Utveckla dialogen mellan universiteten & avnämargrupper i utvecklingen avutbildningar • Skapa regionalt utvecklingslab för bättre samverkan mellan universiteten ochomgivande samhälleInom DARE-projektet kommer nu det material som utvecklats inom framsynsprocessen att användas för utveckling av samverkan inom universiteten, mellan universiteten och med andra intressenter av den regionala utvecklingen, inte minst då de som deltagit i framsynen.
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- Axelsson, Susanna, et al.
(author)
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Economic aspects of the detection of occlusal dentine caries.
- 2009
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In: Acta odontologica Scandinavica. - : Informa UK Limited. - 1502-3850 .- 0001-6357. ; 67:1, s. 38-43
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To evaluate the cost of true-positive occlusal dentine caries detection in permanent molars assessed by: (I) visual-tactile examination, (II) visual-tactile examination combined with bitewing radiographs, and (III) selective radiographic examination of patients with lesions detected clinically. A second aim was to analyse the different strategies when the costs of the subsequent restorative care are considered. METHODS: A model analysis was applied owing to the lack of original articles. Sensitivity and specificity were calculated from a systematic review and included in vitro and in vivo studies of medium and high quality. The direct costs for examinations and restorative care were extracted from the costs of the Public Dental Service in Sweden (2006). RESULTS: The diagnostic costs per true-positive finding were dependent on the occurrence of occlusal caries and increased with decreasing prevalence. The strategy by which radiographs were exposed selectively on the basis of findings from visual-tactile examination resulted in higher initial costs compared with the first and second strategies. When the costs of the subsequent restorative care were added, the selective strategy was most beneficial by up to 26% savings per true-positive diagnosis. However, with this selective strategy, more cases of true-positive dentine caries were assumed would remain undetected as compared with the combined strategy with visual-tactile examination and radiographs for all. CONCLUSIONS: The cost for a true-positive caries diagnosis was inversely related to caries occurrence, and different diagnostic strategies may display contrasting outcomes when subsequent restorative care is taken into account.
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| 8. |
- Baladi, Tom, 1991, et al.
(author)
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Stealth Fluorescence Labeling for Live Microscopy Imaging of mRNA Delivery
- 2021
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In: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 143:14, s. 5413-5424
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Journal article (peer-reviewed)abstract
- Methods for tracking RNA inside living cells without perturbing their natural interactions and functions are critical within biology and, in particular, to facilitate studies of therapeutic RNA delivery. We present a stealth labeling approach that can efficiently, and with high fidelity, generate RNA transcripts, through enzymatic incorporation of the triphosphate of tCO, a fluorescent tricyclic cytosine analogue. We demonstrate this by incorporation of tCO in up to 100% of the natural cytosine positions of a 1.2 kb mRNA encoding for the histone H2B fused to GFP (H2B:GFP). Spectroscopic characterization of this mRNA shows that the incorporation rate of tCO is similar to cytosine, which allows for efficient labeling and controlled tuning of labeling ratios for different applications. Using live cell confocal microscopy and flow cytometry, we show that the tCO-labeled mRNA is efficiently translated into H2B:GFP inside human cells. Hence, we not only develop the use of fluorescent base analogue labeling of nucleic acids in live-cell microscopy but also, importantly, show that the resulting transcript is translated into the correct protein. Moreover, the spectral properties of our transcripts and their translation product allow for their straightforward, simultaneous visualization in live cells. Finally, we find that chemically transfected tCO-labeled RNA, unlike a state-of-the-art fluorescently labeled RNA, gives rise to expression of a similar amount of protein as its natural counterpart, hence representing a methodology for studying natural, unperturbed processing of mRNA used in RNA therapeutics and in vaccines, like the ones developed against SARS-CoV-2.
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| 9. |
- Becquart, Cécile, et al.
(author)
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Intracellular Absolute Quantification of Oligonucleotide Therapeutics by NanoSIMS
- 2022
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In: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 94:29, s. 10549-10556
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Journal article (peer-reviewed)abstract
- Antisense oligonucleotide (ASO)-based therapeutics hold great potential for the treatment of a variety of diseases. Therefore, a better understanding of cellular delivery, uptake, and trafficking mechanisms of ASOs is highly important for early-stage drug discovery. In particular, understanding the biodistribution and quantifying the abundance of ASOs at the subcellular level are needed to fully characterize their activity. Here, we used a combination of electron microscopy and NanoSIMS to assess the subcellular concentrations of a 34S-labeled GalNAc-ASO and a naked ASO in the organelles of primary human hepatocytes. We first cross-validated the method by including a 127I-labeled ASO, finding that the absolute concentration of the lysosomal ASO using two independent labeling strategies gave matching results, demonstrating the strength of our approach. This work also describes the preparation of external standards for absolute quantification by NanoSIMS. For both the 34S and 127I approaches used for our quantification methodology, we established the limit of detection (5 and 2 μM, respectively) and the lower limit of quantification (14 and 5 μM, respectively).
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| 10. |
- Bjerg, Anders, 1982, et al.
(author)
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Higher Risk of Wheeze in Female than Male Smokers. Results from the Swedish GA(2)LEN Study
- 2013
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In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:1
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Journal article (peer-reviewed)abstract
- Background Women who smoke have higher risk of lung function impairment, COPD and lung cancer than smoking men. An influence of sex hormones has been demonstrated, but the mechanisms are unclear and the associations often subject to confounding. This was a study of wheeze in relation to smoking and sex with adjustment for important confounders. Methods In 2008 the Global Allergy and Asthma European Network (GA2LEN) questionnaire was mailed to 45.000 Swedes (age 16–75 years), and 26.851 (60%) participated. “Any wheeze”: any wheeze during the last 12 months. “Asthmatic wheeze”: wheeze with breathlessness apart from colds. Results Any wheeze and asthmatic wheeze was reported by 17.3% and 7.1% of women, vs. 15.8% and 6.1% of men (both p<0.001). Although smoking prevalence was similar in both sexes, men had greater cumulative exposure, 16.2 pack-years vs. 12.8 in women (p<0.001). Most other exposures and characteristics associated with wheeze were significantly overrepresented in men. Adjusted for these potential confounders and pack-years, current smoking was a stronger risk factor for any wheeze in women aged <53 years, adjusted odds ratio (aOR) 1.85 (1.56–2.19) vs. 1.60 (1.30–1.96) in men. Cumulative smoke exposure and current smoking each interacted significantly with female sex, aOR 1.02 per pack-year (p<0.01) and aOR 1.28 (p = 0.04) respectively. Female compared to male current smokers also had greater risk of asthmatic wheeze, aOR 1.53 vs. 1.03, interaction aOR 1.52 (p = 0.02). These interactions were not seen in age ≥53 years. Discussion In addition to the increased risk of COPD and lung cancer female, compared to male, smokers are at greater risk of significant wheezing symptoms in younger age. This became clearer after adjustment for important confounders including cumulative smoke exposure. Estrogen has previously been shown to increase the bioactivation of several compounds in tobacco smoke, which may enhance smoke-induced airway inflammation in fertile women.
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