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| 4. |
- Ramasamy, Adaikalavan, et al.
(author)
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Genome-Wide Association Studies of Asthma in Population-Based Cohorts Confirm Known and Suggested Loci and Identify an Additional Association near HLA
- 2012
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:9, s. e44008-
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Journal article (peer-reviewed)abstract
- Rationale: Asthma has substantial morbidity and mortality and a strong genetic component, but identification of genetic risk factors is limited by availability of suitable studies. Objectives: To test if population-based cohorts with self-reported physician-diagnosed asthma and genome-wide association (GWA) data could be used to validate known associations with asthma and identify novel associations. Methods: The APCAT (Analysis in Population-based Cohorts of Asthma Traits) consortium consists of 1,716 individuals with asthma and 16,888 healthy controls from six European-descent population-based cohorts. We examined associations in APCAT of thirteen variants previously reported as genome-wide significant (P < 5x10(-8)) and three variants reported as suggestive (P < 5 x 10(-7)). We also searched for novel associations in APCAT (Stage 1) and followed-up the most promising variants in 4,035 asthmatics and 11,251 healthy controls (Stage 2). Finally, we conducted the first genome-wide screen for interactions with smoking or hay fever. Main Results: We observed association in the same direction for all thirteen previously reported variants and nominally replicated ten of them. One variant that was previously suggestive, rs11071559 in RORA, now reaches genome-wide significance when combined with our data (P = 2.4x10(-9)). We also identified two genome-wide significant associations: rs13408661 near IL1RL1/IL18R1 (PStage1+Stage2 = 1.1x10(-9)), which is correlated with a variant recently shown to be associated with asthma (rs3771180), and rs9268516 in the HLA region (PStage1+Stage2 = 1.1x10(-8)), which appears to be independent of previously reported associations in this locus. Finally, we found no strong evidence for gene-environment interactions with smoking or hay fever status. Conclusions: Population-based cohorts with simple asthma phenotypes represent a valuable and largely untapped resource for genetic studies of asthma.
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| 5. |
- von Holst, S, et al.
(author)
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Association studies on 11 published colorectal cancer risk loci
- 2010
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In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 103:4, s. 575-580
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Journal article (peer-reviewed)abstract
- BACKGROUND: Recently, several genome-wide association studies (GWAS) have independently found numerous loci at which common single-nucleotide polymorphisms (SNPs) modestly influence the risk of developing colorectal cancer. The aim of this study was to test 11 loci, reported to be associated with an increased or decreased risk of colorectal cancer: 8q23.3 (rs16892766), 8q24.21 (rs6983267), 9p24 (rs719725), 10p14 (rs10795668), 11q23.1 (rs3802842), 14q22.2 (rs4444235), 15q13.3 (rs4779584), 16q22.1 (rs9929218), 18q21.1 (rs4939827), 19q13.1 (rs10411210) and 20p12.3 (rs961253), in a Swedish-based cohort. METHODS: The cohort was composed of 1786 cases and 1749 controls that were genotyped and analysed statistically. Genotype-phenotype analysis, for all 11 SNPs and sex, age of onset, family history of CRC and tumour location, was performed. RESULTS: Of eleven loci, 5 showed statistically significant odds ratios similar to previously published findings: 8q23.3, 8q24.21, 10p14, 15q13.3 and 18q21.1. The remaining loci 11q23.1, 16q22.1, 19q13.1 and 20p12.3 showed weak trends but somehow similar to what was previously published. The loci 9p24 and 14q22.2 could not be confirmed. We show a higher number of risk alleles in affected individuals compared to controls. Four statistically significant genotype-phenotype associations were found; the G allele of rs6983267 was associated to older age, the G allele of rs1075668 was associated with a younger age and sporadic cases, and the T allele of rs10411210 was associated with younger age. CONCLUSIONS: Our study, using a Swedish population, supports most genetic variants published in GWAS. More studies are needed to validate the genotype-phenotype correlations.
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| 6. |
- Ali, M. A. E., et al.
(author)
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Antimicrobial potential of Saccharomyces boulardii extracts and fractions
- 2012
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In: Journal of Applied Sciences Research. - 1816-157X .- 1819-544X. ; 8:8, s. 4537-4543
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Journal article (peer-reviewed)abstract
- Different extracts of viable therapeutic Saccharomyces boulardii cells were evaluated for their antimicrobial activities against Escherichia coli and Candida albicans. Water, methanol, isopropanol, n-butanol and ethanol were used as solvents for extraction. Ethanol-extract exhibited the highest antimicrobial activity towards both strains, followed by water-extract. No antimicrobial activity could be detected on testing methanol-extract towards both strains. Ethanol- and water-extracts, cells remaining after water and ethanol extraction and broth were also tested for their antimicrobial activities against Gram-positive, Gram-negative, non-filamentous and filamentous fungi and showed considerable amounts of antimicrobial activities. Ethanol extracts exhibited the highest antimicrobial activity against all the tested strains, was then fractionated on a Sephadex G-100 column and the obtained fractions were examined using the agar-well diffusion method against Staphylococcus aureus, E.coli, C. albicans and Aspergillus niger. Results obtained indicate the presence of different scattered active fractions with different potencies against the four tested microorganisms. A large scale fermentation process was conducted using a BioFlo benchtop-15L Fermentor/ Bioreactor and the products were evaluated for their antimicrobial activities.
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| 11. |
- Frisch, M, et al.
(author)
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Cultural bias in the AAP's 2012 Technical Report and Policy Statement on male circumcision
- 2013
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In: Pediatrics. - : American Academy of Pediatrics (AAP). - 1098-4275 .- 0031-4005. ; 131:4, s. 796-800
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Journal article (peer-reviewed)abstract
- The American Academy of Pediatrics recently released its new Technical Report and Policy Statement on male circumcision, concluding that current evidence indicates that the health benefits of newborn male circumcision outweigh the risks. The technical report is based on the scrutiny of a large number of complex scientific articles. Therefore, while striving for objectivity, the conclusions drawn by the 8 task force members reflect what these individual physicians perceived as trustworthy evidence. Seen from the outside, cultural bias reflecting the normality of nontherapeutic male circumcision in the United States seems obvious, and the report’s conclusions are different from those reached by physicians in other parts of the Western world, including Europe, Canada, and Australia. In this commentary, a different view is presented by non–US-based physicians and representatives of general medical associations and societies for pediatrics, pediatric surgery, and pediatric urology in Northern Europe. To these authors, only 1 of the arguments put forward by the American Academy of Pediatrics has some theoretical relevance in relation to infant male circumcision; namely, the possible protection against urinary tract infections in infant boys, which can easily be treated with antibiotics without tissue loss. The other claimed health benefits, including protection against HIV/AIDS, genital herpes, genital warts, and penile cancer, are questionable, weak, and likely to have little public health relevance in a Western context, and they do not represent compelling reasons for surgery before boys are old enough to decide for themselves.
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| 12. |
- Goemans, Nathalie M, et al.
(author)
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Systemic administration of PRO051 in Duchenne's muscular dystrophy.
- 2011
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In: The New England journal of medicine. - 1533-4406. ; 364:16, s. 1513-22
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Journal article (other academic/artistic)abstract
- Local intramuscular administration of the antisense oligonucleotide PRO051 in patients with Duchenne's muscular dystrophy with relevant mutations was previously reported to induce the skipping of exon 51 during pre-messenger RNA splicing of the dystrophin gene and to facilitate new dystrophin expression in muscle-fiber membranes. The present phase 1-2a study aimed to assess the safety, pharmacokinetics, and molecular and clinical effects of systemically administered PRO051.
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| 13. |
- Hancock, Dana B, et al.
(author)
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Genome-Wide Joint Meta-Analysis of SNP and SNP-by-Smoking Interaction Identifies Novel Loci for Pulmonary Function
- 2012
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In: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 8:12, s. e1003098-
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Journal article (peer-reviewed)abstract
- Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV1), and its ratio to forced vital capacity (FEV1/FVC). Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV1 and FEV1/FVC across 19 studies (total N = 50,047). We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest PJMA = 5.00×10−11), HLA-DQB1 and HLA-DQA2 (smallest PJMA = 4.35×10−9), and KCNJ2 and SOX9 (smallest PJMA = 1.28×10−8) were associated with FEV1/FVC or FEV1 in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects.
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| 15. |
- Janson, A R, et al.
(author)
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Laparoscopic stoma formation with a prophylactic prosthetic mesh.
- 2010
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In: Hernia. - : Springer. - 1265-4906 .- 1248-9204. ; 14:5, s. 495-498
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Journal article (peer-reviewed)abstract
- BACKGROUND: One year after stoma formation with an open technique, the rate of parastomal hernia is almost 50%. The herniation rate can be reduced to 10% with the use of a prophylactic mesh in a sublay position. For stomas formed with a laparoscopic technique, a surgical method with the use of prophylactic mesh should be sought. METHODS: Patients with a sigmoidostomy created with a laparoscopic technique were provided with a prophylactic large-pore, low-weight mesh in a sublay position. Follow-up examination was carried out after at least 12 months. RESULTS: Between March 2003 and May 2007, a sigmoidostomy was created in 25 patients. The patients' mean age was 65 years (range 31-89), the mean body mass index was 26 (range 21-32) and 15 were female. One stoma necrosis and two minor wound infections occurred. Parastomal hernia was present in 3 of 20 patients (15%) available for follow-up examination after 11-31 months (mean 19). No fistulas or strictures had developed. No mesh infection was noted and no mesh was removed. CONCLUSION: In laparoscopic stoma formation, a prophylactic large-pore, low-weight mesh in a sublay position is an easy and safe procedure associated with a low rate of parastomal hernia.
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| 16. |
- Macsali, F., et al.
(author)
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Menstrual Cycle and Respiratory Symptoms in a General Nordic-Baltic Population
- 2013
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In: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 187:4, s. 366-373
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Journal article (peer-reviewed)abstract
- Rationale :Thereislittleknowledgeofvariationsinrespiratorysymp- tomsduringthemenstrualcycleinageneralpopulation,andpoten- tial modifying factors are not investigated. Objectives : To investigate menstrual cycle variation in respiratory symptomsinalargegeneralpopulation,usingchronobiologymeth- odology, and stratifying by body mass index (BMI), smoking, and asthma status. Methods : A total of 3,926 women with regular cycles less than or equal to 28 days and not taking exogenous sex hormones answered a postalquestionnaire regarding the first day of their last menstrua- tion and respiratory symptoms in the last 3 days. Moving 4-day meanswerecomputedto smoothunevenrecordsof dailysampling; best-fitting 28-day composite cosine curves were applied to each time series to describe rhythmicity. Measurements and Main Results : Significant rhythmic variations over themenstrualcyclewerefoundineachsymptomforallsubjectsand subgroups. Wheezing was higher on cycle Days 10–22, with a mid- cycle dip near the time of putative ovulation (approximately Days 14–16) in most subgroups. Shortness of breath was higher on days 7–21,withadipjustbeforemidcycleinmanysubgroups.Coughwas higher just after putative ovulation for subjects with asthma, BMI greater than or equal to 23 kg/m 2 , and smokers, or just before ovu- lation and menses onset for low symptomatic subgroups. Conclusions : Respiratory symptoms varied significantly during the menstrual cycle and were most frequent from the midluteal to mid- follicular stages, often with a dip near the time of ovulation. The patternsvariedbyBMI,smoking,andasthmastatus.Theserelations linkrespiratorysymptomswithhormonalchangesthroughthemen- strual cycle and imply a potential for individualized chronotherapy for respiratory diseases.
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| 17. |
- Newson, R. B., et al.
(author)
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The association of asthma, nasal allergies, and positive skin prick tests with obesity, leptin, and adiponectin
- 2014
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In: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 44:2, s. 250-260
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Journal article (peer-reviewed)abstract
- BackgroundCross-sectional and longitudinal reports show that obese adults have more asthma than non-obese adults. A proposed mechanism is via effects of adipokines (leptin and adiponectin) on the immune system. ObjectiveWe wished to measure the associations of asthma and other atopic diseases with serum adipokine levels and to find whether the associations with asthma were strong enough to rule out the possibility that they are secondary to the association of fatness measures with asthma. MethodsThe Global Asthma and Allergy Network of Excellence (GA(2)LEN) clinical follow-up survey is a clinical survey, embedded in a larger multi-centre cross-sectional postal survey, involving, with a case/control design, enrichment of the sample with subjects with asthma and chronic rhinosinusitis (CRS). We recorded serum leptin or adiponectin in 845 men and 1110 women in 15 centres and also anthropometric measures of fatness including body mass index and waist/hip ratio, current asthma, and specific skin prick and IgE sensitisation. We used inverse sampling-probability-weighted rank and regression statistics to measure population associations of disease outcomes with adipokines in males and females, adjusting for confounders (area, age, smoking history, and number of elder siblings) and also mutually adjusting associations with adipokines and fatness measures. ResultsOne thousand nine hundred and fifty-five subjects aged 16-77years had information on leptin or adiponectin levels. Leptin and leptin/adiponectin ratio were positively associated with the level of asthma, especially in females (Somers' D of leptin by asthma score, 0.20; 95% CI, 0.08-0.30; P=0.00079). These associations were attenuated after adjusting for confounders and became non-significant after additionally adjusting for fatness measures and multiple comparisons. Conclusions and Clinical RelevanceAsthma levels are positively associated with serum leptin. However, we cannot rule out the possibility that this association is secondary to associations of both with fatness measures.
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| 18. |
- Smit, Lidwien A. M., et al.
(author)
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Transient receptor potential genes, smoking, occupational exposures and cough in adults
- 2012
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In: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 13, s. 26-
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Journal article (peer-reviewed)abstract
- Background: Transient receptor potential (TRP) vanilloid and ankyrin cation channels are activated by various noxious chemicals and may play an important role in the pathogenesis of cough. The aim was to study the influence of single nucleotide polymorphisms (SNPs) in TRP genes and irritant exposures on cough.Methods: Nocturnal, usual, and chronic cough, smoking, and job history were obtained by questionnaire in 844 asthmatic and 2046 non-asthmatic adults from the Epidemiological study on the Genetics and Environment of Asthma (EGEA) and the European Community Respiratory Health Survey (ECRHS). Occupational exposures to vapors, gases, dusts, and/or fumes were assessed by a job-exposure matrix. Fifty-eight tagging SNPs in TRPV1, TRPV4, and TRPA1 were tested under an additive model.Results: Statistically significant associations of 6 TRPV1 SNPs with cough symptoms were found in non-asthmatics after correction for multiple comparisons. Results were consistent across the eight countries examined. Haplotype-based association analysis confirmed the single SNP analyses for nocturnal cough (7-SNP haplotype: p-global = 4.8 x 10(-6)) and usual cough (9-SNP haplotype: p-global = 4.5 x 10(-6)). Cough symptoms were associated with exposure to irritants such as cigarette smoke and occupational exposures (p < 0.05). Four polymorphisms in TRPV1 further increased the risk of cough symptoms from irritant exposures in asthmatics and non-asthmatics (interaction p < 0.05).Conclusions: TRPV1 SNPs were associated with cough among subjects without asthma from two independent studies in eight European countries. TRPV1 SNPs may enhance susceptibility to cough in current smokers and in subjects with a history of workplace exposures.
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| 24. |
- 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
-
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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| 25. |
- Bornehag, Carl-Gustaf, 1957-, et al.
(author)
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The SELMA study : a birth cohort study in Sweden following more than 2000 mother-child pairs
- 2012
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In: Paediatric and Perinatal Epidemiology. - Hoboken, USA : Wiley-Blackwell. - 0269-5022 .- 1365-3016. ; 26:5, s. 456-467
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Journal article (peer-reviewed)abstract
- Background: This paper describes the background, aim and study design for the Swedish SELMA study that aimed to investigate the importance of early life exposure during pregnancy and infancy to environmental factors with a major focus on endocrine disrupting chemicals for multiple chronic diseases/disorders in offspring.Methods: The cohort was established by recruiting women in the 10th week of pregnancy. Blood and urine from the pregnant women and the child and air and dust from home environment from pregnancy and infancy period have been collected. Questionnaires were used to collect information on life styles, socio-economic status, living conditions, diet and medical history.Results: Of the 8394 reported pregnant women, 6658 were invited to participate in the study. Among the invited women, 2582 (39%) agreed to participate. Of the 4076 (61%) non-participants, 2091 women were invited to a non-respondent questionnaire in order to examine possible selection bias. We found a self-selection bias in the established cohort when compared with the non-participant group, e.g. participating families did smoke less (14% vs. 19%), had more frequent asthma and allergy symptoms in the family (58% vs. 38%), as well as higher education among the mothers (51% vs. 36%) and more often lived in single-family houses (67% vs. 60%).Conclusions: These findings indicate that the participating families do not fully represent the study population and thus, the exposure in this population. However, there is no obvious reason that this selection bias will have an impact on identification of environmental risk factors.
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| 26. |
- Burney, Peter, et al.
(author)
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Chronic obstructive pulmonary disease mortality and prevalence : the associations with smoking and poverty-a BOLD analysis
- 2014
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In: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 69:5, s. 465-473
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Journal article (peer-reviewed)abstract
- Background Chronic obstructive pulmonary disease (COPD) is a commonly reported cause of death and associated with smoking. However, COPD mortality is high in poor countries with low smoking rates. Spirometric restriction predicts mortality better than airflow obstruction, suggesting that the prevalence of restriction could explain mortality rates attributed to COPD. We have studied associations between mortality from COPD and low lung function, and between both lung function and death rates and cigarette consumption and gross national income per capita (GNI). Methods National COPD mortality rates were regressed against the prevalence of airflow obstruction and spirometric restriction in 22 Burden of Obstructive Lung Disease (BOLD) study sites and against GNI, and national smoking prevalence. The prevalence of airflow obstruction and spirometric restriction in the BOLD sites were regressed against GNI and mean pack years smoked. Results National COPD mortality rates were more strongly associated with spirometric restriction in the BOLD sites (<60 years: men r(s)=0.73, p=0.0001; women r(s)=0.90, p<0.0001; 60+ years: men r(s)=0.63, p=0.0022; women r(s)=0.37, p=0.1) than obstruction (<60 years: men r(s)=0.28, p=0.20; women r(s)=0.17, p<0.46; 60+ years: men r(s)=0.28, p=0.23; women r(s)=0.22, p=0.33). Obstruction increased with mean pack years smoked, but COPD mortality fell with increased cigarette consumption and rose rapidly as GNI fell below US$ 15 000. Prevalence of restriction was not associated with smoking but also increased rapidly as GNI fell below US$ 15 000. Conclusions Smoking remains the single most important cause of obstruction but a high prevalence of restriction associated with poverty could explain the high 'COPD' mortality in poor countries.
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| 28. |
- Carsin, A. E., et al.
(author)
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Serum Total Immunoglobulin E Is a Surrogate of Atopy in Adult-Onset Asthma: A Longitudinal Study
- 2013
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In: International Archives of Allergy and Immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 160:4, s. 387-392
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Journal article (peer-reviewed)abstract
- Background: Studies have shown that serum total immunoglobulin E (IgE) levels are higher in asthmatics. However, the role of the serum total IgE level, independently from atopy, in adult asthma is not understood. We studied the associations between serum total IgE, the number of sensitizations and the sum of specific IgEs and new-onset asthma using longitudinal data from the European Community Respiratory Health Survey. Methods: Serum total and specific IgE to 4 common inhalant allergens were measured at baseline in 9,175 participants, with a follow-up of 9 years. Individuals with asthma history and/or asthma symptoms were excluded. Atopy was defined as the presence of at least one specific IgE >= 0.35 kU/l. Total and specific IgEs were regressed against new-onset asthma using multivariate logistic regression with a random intercept for the study centre. Results: Two hundred and ninety-seven participants had developed asthma during follow-up (incidence rate 5.7 per 1,000 person- years). A 10% higher level of total IgE was associated with a 12% increased risk of new-onset asthma (p = 0.005). However, after adjustment for the number of positive specific IgEs [odds ratio (OR) for multiple sensitization 1.74, 95% confidence interval (CI) 1.05-2.88] and the sum of allergen-specific IgEs (OR 1.18, 95% CI 1.00-1.40), the association between total IgE and asthma disappeared (OR 1.00, 95% CI 0.91-1.10). Seventeen percent of new-onset asthma cases could be attributed to atopy, and this estimate was not largely modified when the total IgE level was simultaneously taken into account. Conclusions: After taking into account the number and intensity of 4 specific IgEs, the serum total IgE level was not associated with new-onset asthma in adults.
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| 30. |
- Dahlgren, Markus K, et al.
(author)
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Synthesis of 2-(2-Aminopyrimidine)-2,2-difluoroethanols as Potential Bioisosters of Salicylidene Acylhydrazides
- 2010
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In: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 15:6, s. 4207-12
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Journal article (peer-reviewed)abstract
- Salicylidene acylhydrazides are inhibitors of type III secretion in several Gramnegative pathogens. To further develop the salicylidene acylhydrazides, scaffold hopping was applied to replace the core fragment of the compounds. The novel 2-(2-aminopyrimidine)-2,2-difluoroethanol scaffold was identified as a possible analog to thesalicylidene acylhydrazide core structure. The synthesis of a library of 2-(2-aminopyrimidine)-2,2-difluoro-ethanols is described in this paper.
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| 31. |
- Ek, A., et al.
(author)
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Chronic rhinosinusitis in asthma is a negative predictor of quality of life: results from the Swedish GA(2)LEN survey
- 2013
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In: Allergy. - : Wiley. - 0105-4538 .- 1398-9995. ; 68:10, s. 1314-1321
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Journal article (peer-reviewed)abstract
- BackgroundAsthma and chronic rhinosinusitis (CRS) both impair quality of life, but the quality-of-life impact of comorbid asthma and CRS is poorly known. The aim of this study was to evaluate the impact of CRS and other relevant factors on quality of life in asthmatic subjects. MethodsThis Swedish cohort (age 17-76years) consists of 605 well-characterized asthmatics with and without CRS, 110 individuals with CRS only, and 226 controls and is part of the Global Allergy and Asthma European Network (GA(2)LEN) survey. The Mini Asthma Quality of Life Questionnaire (mAQLQ), the Euro Quality of Life (EQ-5D) health questionnaire, spirometry, skin prick test (SPT), exhaled nitric oxide (FeNO), smell test, and peak nasal inspiratory flow were used. ResultsSubjects having both asthma and CRS have lower mAQLQ scores in all domains (P<0.001) and a lower EQ-5D index value and EQ-5D VAS value (P<0.001) compared to those with asthma only. Asthmatics with CRS have significantly lower FEV1%pred and FVC%pred (88.4 [85.1-91.7] and 99.9 [96.7-103.0], respectively) compared with asthma only (91.9 [90.3-93.4] and 104.0 [102.5-105.5], respectively P<0.05). Multiple regression analysis shows that low asthma quality of life is associated with having CRS (P<0.0001), lower lung function (P=0.008), current smoking (P=0.01), BMI>30kg/m(2) (P=0.04), high age (P=0.03), and a negative SPT (P=0.04). ConclusionsComorbid CRS was a significant and independent negative predictor of quality of life in asthmatics. Other negative factors were lower lung function, current smoking, obesity, advanced age, and having nonatopic asthma.
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| 32. |
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| 33. |
- Emilsson, Ossur I., et al.
(author)
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Nocturnal gastro-oesophageal reflux, asthma and symptoms of OSA : a longitudinal, general population study
- 2013
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In: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 41:6, s. 1347-1354
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Journal article (peer-reviewed)abstract
- Nocturnal gastro-oesophageal reflux (nGOR) is associated with asthma and obstructive sleep apnoea (OSA). Our aim was to investigate whether nGOR is a risk factor for onset of asthma and onset of respiratory and OSA symptoms in a prospective population-based study. We invited 2640 subjects from Iceland, Sweden and Belgium for two evaluations over a 9-year interval. They participated in structured interviews, answered questionnaires, and underwent spirometries and methacholine challenge testing. nGOR was defined by reported symptoms. Subjects with persistent nGOR (n=123) had an independent increased risk of new asthma at follow-up (OR 2.3, 95% CI 1.1-4.9). Persistent nGOR was independently related to onset of respiratory symptoms (OR 3.0, 95% CI 1.6-5.6). The risk of developing symptoms of OSA was increased in subjects with new and persistent nGOR (OR 2.2, 95% CI 1.3-1.6, and OR 2.0, 95% CI 1.0-3.7, respectively). No significant association was found between nGOR and lung function or bronchial responsiveness. Persistent symptoms of nGOR contribute to the development of asthma and respiratory symptoms. New onset of OSA symptoms is higher among subjects with symptoms of nGOR. These findings provide evidence that nGOR may play a role in the genesis of respiratory symptoms and diseases.
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| 34. |
- Fjalldal, Sigridur B., et al.
(author)
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Smoking, stages of change and decisional balance in Iceland and Sweden
- 2011
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In: The Clinical Respiratory Journal. - 1752-6981. ; 5:2, s. 76-83
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Journal article (peer-reviewed)abstract
- Introduction: Smoking remains a significant health problem. Smoking interventions are important but selection of successful quitters can be difficult. Objective: To characterise smokers with emphasis on two constructs of the transtheoretical model, the stages of change and decisional balance. Methods: A random sample from adults aged 40 and over in Reykjavik, Iceland, and Uppsala, Sweden. Smokers were defined as being in the stage of pre-contemplation (not thinking of quitting within the next 6 months), contemplation (thinking of quitting within the next 6 months) or preparation (thinking of quitting within the next 30 days, having managed to quit for at least 24 h within the last 12 months). Results: A total of 226 participants were smokers: 72 (32%) were in the pre-contemplation stage, 126 (56%) in the contemplation stage and 28 (12%) in the preparation stage. A younger age, higher body mass index (BMI) and higher educational level were significantly related to being in a more advanced stage. A significant association was observed between decisional balance and stages of change such that decreased importance of the positive aspects of smoking and increased importance of the negative aspects of smoking were independently associated with an increased readiness to quit. Conclusion: The motivated smoker is likely to be young and educated with an above average BMI. A smoker in the contemplation stage is likely to maintain the negative aspects of smoking at a high level. Decreasing the value of the pros of smoking may facilitate the shift towards the stage of preparation.
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| 35. |
- Forsberg, Lars A., et al.
(author)
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Mosaic loss of chromosome Y in peripheral blood is associated with shorter survival and higher risk of cancer
- 2014
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:6, s. 624-628
-
Journal article (peer-reviewed)abstract
- Incidence and mortality for sex-unspecific cancers are higher among men, a fact that is largely unexplained(1,2). Furthermore, age-related loss of chromosome Y (LOY) is frequent in normal hematopoietic cells(3,4), but the phenotypic consequences of LOY have been elusive(5-10). From analysis of 1,153 elderly men, we report that LOY in peripheral blood was associated with risks of all-cause mortality (hazards ratio (HR) = 1.91, 95% confidence interval (CI) = 1.17-3.13; 637 events) and non-hematological cancer mortality (HR = 3.62, 95% CI = 1.56-8.41; 132 events). LOY affected at least 8.2% of the subjects in this cohort, and median survival times among men with LOY were 5.5 years shorter. Association of LOY with risk of all-cause mortality was validated in an independent cohort (HR = 3.66) in which 20.5% of subjects showed LOY. These results illustrate the impact of post-zygotic mosaicism on disease risk, could explain why males are more frequently affected by cancer and suggest that chromosome Y is important in processes beyond sex determination. LOY in blood could become a predictive biomarker of male carcinogenesis.
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| 36. |
- Gilbert, R. E., et al.
(author)
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Trends in child maltreatment reply
- 2012
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In: The Lancet. - New York, USA : Elsevier. - 0140-6736 .- 1474-547X. ; 379:9831, s. 2049-2049
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Journal article (peer-reviewed)
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| 37. |
- Golparian, Daniel, 1984-, et al.
(author)
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Four treatment failures of pharyngeal gonorrhoea with ceftriaxone (500 mg) or cefotaxime (500 mg), Sweden, 2013 and 2014
- 2014
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In: Eurosurveillance. - : European Centre for Disease Prevention and Control (ECDC). - 1025-496X .- 1560-7917. ; 19:30, s. 2-5
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Journal article (peer-reviewed)abstract
- We describe four cases in Sweden of verified treatment failures of pharyngeal gonorrhoea with ceftriaxone (500 mg; n=3) or cefotaxime (500 mg; n=1) monotherapy. All the ceftriaxone treatment failures were caused by the internationally spreading multidrug-resistant gonococcal NG-MAST genogroup 1407 clone. Increased awareness of treatment failures is crucial particularly when antimicrobial monotherapy is used. Frequent test of cure and appropriate verification/falsification of suspected treatment failures, as well as implementation of recommended dual antimicrobial therapy are imperative.
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| 38. |
- Janson, Staffan, 1945-, et al.
(author)
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How can we improve child health services?
- 2011
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In: The BMJ. - : BMJ Books. - 1756-1833. ; 342, s. 901-904
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Journal article (peer-reviewed)abstract
- Western European health systems are not keeping pace with changes in child health needs. Non-communicable diseases are increasingly common causes of childhood illness and death. Countries are responding to changing needs by adapting child health services in different ways and useful insights can be gained through comparison, especially because some have better outcomes, or have made more progress, than others. Although overall child health has improved throughout Europe, wide inequities remain. Health services and social and cultural determinants contribute to differences in health outcomes. Improvement of child health and reduction of suffering are achievable goals. Development of systems more responsive to evolving child health needs is likely to necessitate reconfiguring of health services as part of a whole-systems approach to improvement of health. Chronic care services and first-contact care systems are important aspects. The Swedish and Dutch experiences of development of integrated systems emphasise the importance of supportive policies backed by adequate funding. France, the UK, Italy, and Germany offer further insights into chronic care services in different health systems. First-contact care models and the outcomes they deliver are highly variable. Comparisons between systems are challenging. Important issues emerging include the organisation of first-contact models, professional training, arrangements for provision of out-of-hours services, and task-sharing between doctors and nurses. Flexible first-contact models in which child health professionals work closely together could offer a way to balance the need to provide expertise with ready access. Strategies to improve child health and health services in Europe necessitate a whole-systems approach in three interdependent systems—practice (chronic care models, first-contact care, competency standards for child health professionals), plans (child health indicator sets, reliable systems for capture and analysis of data, scale-up of child health research, anticipation of future child health needs), and policy (translation of high-level goals into actionable policies, open and transparent accountability structures, political commitment to delivery of improvements in child health and equity throughout Europe).
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| 39. |
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| 40. |
- Jerlhag, Elisabeth, 1978, et al.
(author)
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Concomitant Release of Ventral Tegmental Acetylcholine and Accumbal Dopamine by Ghrelin in Rats
- 2012
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In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 7:11
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Journal article (peer-reviewed)abstract
- Ghrelin, an orexigenic peptide, regulates energy balance specifically via hypothalamic circuits. Growing evidence suggest that ghrelin increases the incentive value of motivated behaviours via activation of the cholinergic-dopaminergic reward link. It encompasses the cholinergic afferent projection from the laterodorsal tegmental area (LDTg) to the dopaminergic cells of the ventral tegmental area (VTA) and the mesolimbic dopamine system projecting from the VTA to nucleus accumbens (N.Acc.). Ghrelin receptors (GHS-R1A) are expressed in these reward nodes and ghrelin administration into the LDTg increases accumbal dopamine, an effect involving nicotinic acetylcholine receptors in the VTA. The present series of experiments were undertaken directly to test this hypothesis. Here we show that ghrelin, administered peripherally or locally into the LDTg concomitantly increases ventral tegmental acetylcholine as well as accumbal dopamine release. A GHS-R1A antagonist blocks this synchronous neurotransmitter release induced by peripheral ghrelin. In addition, local perfusion of the unselective nicotinic antagonist mecamylamine into the VTA blocks the ability of ghrelin (administered into the LDTg) to increase N.Acc.-dopamine, but not VTA-acetylcholine. Collectively our data indicate that ghrelin activates the LDTg causing a release of acetylcholine in the VTA, which in turn activates local nicotinic acetylcholine receptors causing a release of accumbal dopamine. Given that a dysfunction in the cholinergic-dopaminergic reward system is involved in addictive behaviours, including compulsive overeating and alcohol use disorder, and that hyperghrelinemia is associated with such addictive behaviours, ghrelin-responsive circuits may serve as a novel pharmacological target for treatment of alcohol use disorder as well as binge eating.
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| 41. |
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| 42. |
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| 43. |
- Malinovschi, Andrei, et al.
(author)
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Exhaled nitric oxide levels and blood eosinophil counts independently associate with wheeze and asthma events in National Health and Nutrition Examination Survey subjects
- 2013
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In: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 132:4, s. 821-
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Journal article (peer-reviewed)abstract
- Background: Fraction of exhaled nitric oxide (FENO) and blood eosinophil count (B-Eos) values, markers of local and systemic eosinophilic inflammation, respectively, are increased in asthmatic patients. Little is known about the relation of these markers to reportedwheeze and asthma events in a random population sample. Objectives: We sought to determine the individual and independent values of B-Eos and FENO in relation to wheeze, asthma diagnosis, and asthma events in a cross-sectional study. Methods: FENO and B-Eos values were measured in 12,408 subjects aged 6 to 80 years from the National Health and Nutrition Examination Survey 2007-2008 and 2009-2010. Current wheeze and asthma diagnosis, as well as asthma attacks and asthma-related emergency department (ED) visits within the last 12 months, were assessed by means of questionnaires. Results: Intermediate or high FENO values and intermediate or high B-Eos values were independently associated with having asthma, wheeze, and asthma attacks. However, only intermediate and high B-Eos values were independently associated with asthma-related ED visits. High FENO (>= 50 ppb) and B-Eos (>= 500 cells/ mm(3)) values rendered an adjusted odds ratio of 4.5 of having wheeze, 5.1 of having asthma, 5.4 for asthma attacks, and 2.9 for asthma-related ED visits compared with normal FENO (< 25 ppb) and B-Eos (< 300 cells/ mm(3)) values. Conclusions: Exhaled nitric oxide and B-Eos values offered independent information in relation to the prevalence of wheeze, asthma diagnosis, and asthma events in this random population sample. The clinical importance of these findings in asthmatic patients with regard to phenotyping and individualized treatment, considering both local and systemic eosinophilic inflammation, needs to be determined.
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| 44. |
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| 45. |
- Marcon, A., et al.
(author)
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Can an airway challenge test predict respiratory diseases? A population-based international study
- 2014
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In: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 133:1
-
Journal article (peer-reviewed)abstract
- Background: Evidence on the longitudinal association of airway responsiveness with respiratory diseases is scarce. The best indicator of responsiveness is still undetermined. Objective: We investigated the association of airway responsiveness with the incidence of asthma, chronic obstructive pulmonary disease (COPD), and allergic rhinitis. Methods: We studied 3851 subjects who underwent spirometry and methacholine challenge tests both at baseline (1991-1993), when they were 20 to 44 years old, and at follow-up (1999-2002) in the European Community Respiratory Health Survey. Airway responsiveness was defined based on the methacholine dose-response slope on both occasions. Incidence rate ratios for the association of airway responsiveness with disease occurrence were computed by using Poisson regression. Results: With respect to reference (slope of the fourth quintile or greater), subjects with the greatest degree of airway responsiveness (slope less than the first quintile) showed the greatest risk of developing asthma, COPD, and allergic rhinitis (incidence rate ratios of 10.82, 5.53, and 4.84, respectively; all P <.01). A low slope predicted disease occurrence, even in subjects who did not reach a 20% decrease in FEV1 at the cumulative dose of 1 mg of methacholine (PD20 >1 mg). A decrease in slope over time was an independent predictor of disease risk. Conclusion: Airway responsiveness predicted new-onset asthma, COPD, and allergic rhinitis. Our study supports the use of a continuous noncensored indicator of airway responsiveness, such as the slope of the methacholine dose-response curve, in clinical practice and research because it showed clear advantages over PD20. © 2013 American Academy of Allergy, Asthma & Immunology.
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| 46. |
- Nilsson, Gisela M A, 1973, et al.
(author)
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Loss of E-cadherin expression is not a prerequisite for c-erbB2-induced epithelial-mesenchymal transition.
- 2014
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In: International journal of oncology. - : Spandidos Publications. - 1791-2423 .- 1019-6439. ; 45:1, s. 82-94
-
Journal article (peer-reviewed)abstract
- Recent research into the mechanisms of tumour cell invasiveness has highlighted the parallels between carcinogenesis and epithelial-mesenchymal transition (EMT), originally described as a developmental transdifferentiation program but also implicated in fibrosis and cancer. In a model system for mammary carcinogenesis, we previously observed that induced signalling from a homodimer of the c-erbB2 (HER2) receptor tyrosine kinase in an initially non-malignant mammary cell line caused EMT where i)cell scattering occurred before downregulation of the cell-cell adhesion molecule E-cadherin and ii)the progress of EMT was dramatically delayed when cells were grown at high density. Here, we have further analysed these phenomena. Ectopic expression of E-cadherin concomitant with c-erbB2 signalling was unable to impede the progression of EMT, suggesting that E-cadherin downregulation is not required for EMT. Furthermore, fibroblast-like cells isolated after EMT induced in the presence or absence of ectopic E-cadherin expression showed highly similar morphology and vimentin expression. E-cadherin expressed in these fibroblastic cells had a subcellular localisation similar to that found in epithelial cells, but it exhibited a much weaker attachment to the cytoskeleton, suggesting cytoskeletal rearrangements as an important mechanism in EMT-associated cell scattering. We also investigated whether density-dependent inhibition of EMT is mediated by E-cadherin as a sensor for cell-cell contact, by expressing dominant-negative E-cadherin. While expression of this mutant weakened cell-cell adhesion, it failed to facilitate EMT at high cell densities. These results indicate that loss of E-cadherin expression is a consequence rather than a cause of c-erbB2-induced EMT and that density‑dependent inhibition of EMT is not mediated by E-cadherin signalling.
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| 47. |
- Obaseki, D., et al.
(author)
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The relation of airway obstruction to asthma, chronic rhinosinusitis and age: results from a population survey of adults
- 2014
-
In: Allergy. - : Wiley. - 0105-4538 .- 1398-9995. ; 69:9, s. 1205-1214
-
Journal article (peer-reviewed)abstract
- Rationale: There is conflicting evidence on whether patients with asthma experience an accelerated decline in lung function with age. We examined the association between postbronchodilator lung function, asthma, chronic rhinosinusitis (CRS), and atopy with age using a large European sample. Methods: In 17 centers in 11 European countries, case control studies were nested within representative cross-sectional surveys of adults aged less than 75 years. Representative samples of participants with asthma, CRS or both and controls were assessed for postbronchodilator ventilatory function, smoking history, atopy, and treatment. Multiple regression was used to assess the interactive effects of age and diagnostic group on decline in postbronchodilator ventilatory function. Results: A total of 3337 participants provided adequate data (778 with asthma, 399 with CRS, 244 with both asthma and CRS and 1916 controls who had neither asthma nor CRS). Participants with asthma had lower FEV1/FVC (-4.09% (95% CI: -5.02, -3.15, P < 0.001) and a steeper slope of FEV1/FVC against age (-0.14%/annum [95%CI: -0.19, -0.08]) equivalent to smoking 1-2 packs of cigarettes per day. Those with atopy had a slope equivalent to controls. Conclusions: People with asthma have a steeper decline in postbronchodilator lung function with age, but neither CRS nor atopy alone were associated with such decline.
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| 48. |
- Rebordosa, C, et al.
(author)
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ADRB2 Gly16Arg polymorphism, asthma control and lung function decline
- 2011
-
In: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 38:5, s. 1029-1035
-
Journal article (peer-reviewed)abstract
- Arg/Arg homozygotes for the Gly16Arg polymorphism in the β(2)-adrenoreceptor gene (ADRB2) have a reduced response to short-acting β(2)-agonists but no effect has been associated with long-acting β(2)-agonists (LABAs). We selected 604 subjects with current asthma from the European Community Respiratory Health Study to evaluate whether asthma control and lung function decline were associated with Gly16Arg polymorphism, and to test whether LABA or inhaled corticosteroid (ICS) use modified these effects. There was an increased risk of noncontrolled asthma (OR 1.33, 95% CI 1.01-1.75; p=0.046) for each Arg allele. Among nonusers of ICS, the odds ratio of noncontrolled asthma among Arg/Arg versus Gly/Gly subjects was 2.73 (95% CI 1.28-5.82; p=0.009). No increased risk of noncontrolled asthma associated with the Arg allele was observed among ICS and/or LABA users. For each Arg allele, a mean±se decrease in decline in forced expiratory volume in 1 s of 7.7±2.5 mL·yr(-1) was found (p-value for trend 0.003), irrespective of ICS or LABA use. Arg/Arg subjects had an increased risk of bronchial hyperresponsiveness (BHR) versus Gly/Gly subjects, with an odds ratio of 2.51 (95% CI 1.12-5.63; p=0.025) if they did not use ICS. The Arg allele was associated with poorer asthma control, a steeper lung function decline and BHR. Absence of genotypic effects on asthma control among ICS users may be due to reversed β(2)-adrenoreceptor desensitisation.
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| 49. |
- Sahlberg, Bo, et al.
(author)
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Airborne molds and bacteria, microbial volatile organic compounds (MVOC), plasticizers and formaldehyde in dwellings in three North European cities in relation to sick building syndrome (SBS)
- 2013
-
In: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 444, s. 433-440
-
Journal article (peer-reviewed)abstract
- There are few studies on associations between airborne microbial exposure, formaldehyde, plasticizers in dwellings and the symptoms compatible with the sick building syndrome (SBS). As a follow-up of the European Community Respiratory Health Survey (ECRHS II), indoor measurements were performed in homes in three North European cities. The aim was to examine whether volatile organic compounds of possible microbial origin (MVOCs), and airborne levels of bacteria, molds, formaldehyde, and two plasticizers in dwellings were associated with the prevalence of SBS, and to study associations between MVOCs and reports on dampness and mold.The study included homes from three centers included in ECRHS II. A total of 159 adults (57% females) participated (19% from Reykjavik, 40% from Uppsala, and 41% from Tartu). A random sample and additional homes with a history of dampness were included. Exposure measurements were performed in the 159 homes of the participants. MVOCs were analyzed by GCMS with selective ion monitoring (SIM). Symptoms were reported in a standardized questionnaire. Associations were analyzed by multiple logistic regression.In total 30.8% reported any SBS (20% mucosal, 10% general, and 8% dermal symptoms) and 41% of the homes had a history of dampness and molds There were positive associations between any SBS and levels of 2-pentanol (P=0.002), 2-hexanone (P=0.0002), 2-pentylfuran (P=0.009), 1-octen-3-ol (P=0.002), formaldehyde (P=0.05), and 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate (Texanol) (P=0.05). 1-octen-3-ol (P=0.009) and 3-methylfuran (P=0.002) were associated with mucosal symptoms. In dwellings with dampness and molds, the levels of total bacteria (P=0.02), total mold (P=0.04), viable mold (P=0.02), 3-methylfuran (P=0.008) and ethyl-isobutyrate (P=0.02) were higher.In conclusion, some MVOCs like 1-octen-3-ol, formaldehyde and the plasticizer Texanol, may be a risk factor for sick building syndrome. Moreover, concentrations of airborne molds, bacteria and some other MVOCs were slightly higher in homes with reported dampness and mold.
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| 50. |
- Shum, Anthony K., et al.
(author)
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BPIFB1 Is a Lung-Specific Autoantigen Associated with Interstitial Lung Disease
- 2013
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In: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 5:206, s. 206ra139-
-
Journal article (peer-reviewed)abstract
- Interstitial lung disease (ILD) is a complex and heterogeneous disorder that is often associated with autoimmune syndromes. Despite the connection between ILD and autoimmunity, it remains unclear whether ILD can develop from an autoimmune response that specifically targets the lung parenchyma. We examined a severe form of autoimmune disease, autoimmune polyglandular syndrome type 1 (APS1), and established a strong link between an autoimmune response to the lung-specific protein BPIFB1 (bactericidal/permeability-increasing fold-containing B1) and clinical ILD. Screening of a large cohort of APS1 patients revealed autoantibodies to BPIFB1 in 9.6% of APS1 subjects overall and in 100% of APS1 subjects with ILD. Further investigation of ILD outside the APS1 disorder revealed BPIFB1 autoantibodies present in 14.6% of patients with connective tissue disease-associated ILD and in 12.0% of patients with idiopathic ILD. The animal model for APS1, Aire(-/-) mice, harbors autoantibodies to a similar lung antigen (BPIFB9); these autoantibodies are a marker for ILD. We found that a defect in thymic tolerance was responsible for the production of BPIFB9 autoantibodies and the development of ILD. We also found that immunoreactivity targeting BPIFB1 independent of a defect in Aire also led to ILD, consistent with our discovery of BPIFB1 autoantibodies in non-APS1 patients. Overall, our results demonstrate that autoimmunity targeting the lung-specific antigen BPIFB1 may contribute to the pathogenesis of ILD in patients with APS1 and in subsets of patients with non-APS1 ILD, demonstrating the role of lung-specific autoimmunity in the genesis of ILD.
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