Ryanodine receptors: physiological function and deregulation in Alzheimer disease

BackgroundHealth-care professionals have a responsibility to be attentive to patients’ adherence behavior but it could be difficult to identify poor adherence in the context of clinical practice. Assessment of personality could be used to identify individuals who are in need for support with their adherence behavior. To our knowledge, existing adherence questionnaires are not based on individuals reflecting asthmatics in the general population and there is limited research describing adherence with asthma medication in relation to personal goals with the treatment. The aim was to develop and validate an adherence questionnaire in adult individuals with asthma from the general population and to assess adherence in relation to personality traits and goals with the asthma medication using the developed questionnaire.MethodsThe study was conducted in three phases: 1. A preliminary postal 46-item questionnaire was refined after psychometric testing (n = 157). 2. The questionnaire was validated (n = 104). 3. The developed adherence questionnaire was analyzed in relation to personality traits and achieved goals with the asthma medication. Adult respondents with physician diagnosed asthma using asthma medications were selected from the population-based West Sweden Asthma Study. The respondents completed the Neuroticism, Extraversion and Openness to Experience Five-Factor Inventory and the Medication Adherence Report Scale and stated their goals with the asthma medication. Data were analyzed using t-tests, correlations, multiple regression and principal component analysis.ResultsA final questionnaire was developed consisting of ten items organized in three subscales - “medication routines”, “self-adjusting the medication” and “concerns about side-effects”. Two of the subscales - “medication routines” and “self-adjusting the medication” – were associated with the Medication Adherence Report Scale. The subscale “medication routines” was associated with the personality traits – Conscientiousness and Neuroticism and unachieved goals with the asthma medication.ConclusionsThe developed questionnaire appears to be useful for measuring adherence to asthma medication in adult individuals with asthma. The study suggests that both individual differences and personal treatment goals need to be addressed in efforts to promote adherence to asthma medication treatment

The Significance of Asthma Follow-Up Consultations for Adherence to Asthma Medication, Asthma Medication Beliefs, and Asthma Control

Objective. The aim was to investigate adherence to asthma medication treatment, medication beliefs, and asthma control in relation to asthma follow-up consultations in asthmatics in the general population. A further aim was to describe associations between adherence, medication beliefs, and asthma control. Method. In the population-based West Sweden Asthma Study, data allowing calculation of adherence for 4.5 years based on pharmacy records were obtained from 165 adult asthmatics. Additional data were collected through questionnaires and structured interviews. Results. The mean adherence value for filled prescriptions for regular asthma medication was 68% (median 55.3%) but varied over the year under study. Adherence to combination inhalers with corticosteroids and long-acting beta 2 agonists was higher than adherence to single inhalers with corticosteroids only. More than one-third of participants reported not having seen an asthma nurse or physician for several years. Regular asthma followup consultations were associated with both higher adherence and the belief that asthma medication was necessary but were not associated with asthma control. Conclusions. Adherence to asthma medication treatment was low and varied over the year under study. The current study suggests that quality improvements in asthma care are needed if adherence to asthma medication is to be improved

Network analysis of quantitative proteomics on asthmatic bronchi: effects of inhaled glucocorticoid treatment

<p>Abstract</p> <p>Background</p> <p>Proteomic studies of respiratory disorders have the potential to identify protein biomarkers for diagnosis and disease monitoring. Utilisation of sensitive quantitative proteomic methods creates opportunities to determine individual patient proteomes. The aim of the current study was to determine if quantitative proteomics of bronchial biopsies from asthmatics can distinguish relevant biological functions and whether inhaled glucocorticoid treatment affects these functions.</p> <p>Methods</p> <p>Endobronchial biopsies were taken from untreated asthmatic patients (<it>n </it>= 12) and healthy controls (<it>n </it>= 3). Asthmatic patients were randomised to double blind treatment with either placebo or budesonide (800 μg daily for 3 months) and new biopsies were obtained. Proteins extracted from the biopsies were digested and analysed using isobaric tags for relative and absolute quantitation combined with a nanoLC-LTQ Orbitrap mass spectrometer. Spectra obtained were used to identify and quantify proteins. Pathways analysis was performed using Ingenuity Pathway Analysis to identify significant biological pathways in asthma and determine how the expression of these pathways was changed by treatment.</p> <p>Results</p> <p>More than 1800 proteins were identified and quantified in the bronchial biopsies of subjects. The pathway analysis revealed acute phase response signalling, cell-to-cell signalling and tissue development associations with proteins expressed in asthmatics compared to controls. The functions and pathways associated with placebo and budesonide treatment showed distinct differences, including the decreased association with acute phase proteins as a result of budesonide treatment compared to placebo.</p> <p>Conclusions</p> <p>Proteomic analysis of bronchial biopsy material can be used to identify and quantify proteins using highly sensitive technologies, without the need for pooling of samples from several patients. Distinct pathophysiological features of asthma can be identified using this approach and the expression of these features is changed by inhaled glucocorticoid treatment. Quantitative proteomics may be applied to identify mechanisms of disease that may assist in the accurate and timely diagnosis of asthma.</p> <p>Trial registration</p> <p>ClinicalTrials.gov registration <a href="http://www.clinicaltrials.gov/ct2/show/NCT01378039">NCT01378039</a></p

About the necessity of the linguacultural aspect in teaching English

В статье на примере отдельных английских и русских фразеологизмов иллюстрируется репродукция в языке, в частности, в его фразеологическом фонде, культурологических особенностей, обусловленных экстралингвистическими факторами. Подчеркивается необходимость изучения определенного языка с обязательным учетом лингвокультурологического аспекта.The article illustrates the reproduction of cultural features in a language, in particular, in its phraseological fund, due to extralinguistic factors, on the example of the English and Russian phraseological units. The necessity of studying a certain language with the obligatory consideration of the linguoculturological aspect is emphasized

Differences in diagnostic patterns of obstructive airway disease between areas and sex in Sweden and Finland-the Nordic EpiLung study

Objective:To investigate the current prevalence of physician-diagnosed obstructive airway diseases by respiratory symptoms and by sex in Sweden and Finland. Method:In 2016, a postal questionnaire was answered by 34,072 randomly selected adults in four study areas: Vastra Gotaland and Norrbotten in Sweden, and Seinajoki-Vaasa and Helsinki in Finland. Results:The prevalence of asthma symptoms was higher in Norrbotten (13.2%), Seinajoki-Vaasa (14.8%) and Helsinki (14.4%) than in Vastra Gotaland (10.7%), and physician-diagnosed asthma was highest in Norrbotten (13.0%) and least in Vastra Gotaland (10.1%). Chronic productive cough was most common in the Finnish areas (7.7-8.2% versus 6.3-6.7%) while the prevalence of physician-diagnosed chronic bronchitis (CB) or chronic obstructive pulmonary disease (COPD) varied between 1.7 and 2.7% in the four areas. Among individuals with respiratory symptoms, the prevalence of asthma was most common in Norrbotten, while a diagnosis of COPD or CB was most common in Vastra Gotaland and Seinajoki-Vaasa. More women than men with respiratory symptoms reported a diagnosis of asthma in Sweden and Seinajoki-Vaasa but there were no sex differences in Helsinki. In Sweden, more women than men with symptoms of cough or phlegm reported a diagnosis of CB or COPD, while in Finland the opposite was found. Conclusion:The prevalence of respiratory symptoms and corresponding diagnoses varied between and within the countries. The proportion reporting a diagnosis of obstructive airway disease among individuals with respiratory symptoms varied, indicating differences in diagnostic patterns both between areas and by sex.Peer reviewe

Smoking Is Associated With Low Levels of Soluble PD-L1 in Rheumatoid Arthritis

BackgroundSmoking is a risk factor for developing rheumatoid arthritis (RA), but the mechanism remains uncertain. We previously demonstrated that smoking lowers the T cell activation threshold by limiting programmed death protein 1 (PD-1) expression.AimTo investigate how smoking influence the levels of soluble PD-1 ligand (sPD-L1).MethodSerum levels of sPD-L1 were measured in 246 RA patients and in 168 healthy subjects. The analysis was done with respect to inflammation, smoking, treatments, and autoantibody status. The effect of therapeutic TNF-inhibiting antibodies (TNFi) on sPD-L1 was studied in 16 RA patients at their first infliximab infusion. The expression of Fcγ-receptor (FcγR) subclass IIB and IIIA was analyzed with quantitative polymerase chain reaction in peripheral blood mononuclear cells (PBMCs) from 12 RA patients and 15 healthy controls, and in healthy PBMC exposed to IgG containing antibodies to cyclic citrullinated peptides (aCCP).ResultsThe negative association between smoking and sPD-L1 in RA patients was established by multiple logistic regression (OR = 0.52, p = 0.038). Other covariates in the regression model were serum levels of IL-1β representing inflammation (OR = 1.6, p = 0.0076) and aCCP positivity (OR = 1.9, p = 0.047). First infliximab infusion repressed sPD-L1 (p = 0.023) in patients, and low levels of sPD-L1 were found in patients with early RA treated with TNFi (p = 0.018). Treatment with TNFi was associated with higher sPD-L1 in patients with long disease duration (p = 0.041) and restored levels in smokers. In vitro exposure to aCCP+ IgG suppressed sPD-L1 (p = 0.036), but aCCP+ patients with long disease duration had higher sPD-L1 (p = 0.016). High ratio of the inhibitory FcγR subclass IIB over the stimulatory IIIA resulted in low sPD-L1 release (p = 0.029). Smoking was associated with a higher FcγR IIB/IIIA ratio (p = 0.00062) and lower levels of sPD-L1 (p = 0.013).ConclusionIn RA, serum sPD-L1 was related to systemic inflammation and aCCP positivity. Smoking altered the expression of FcγRs and limited sPD-L1 in RA patients, permitting inappropriate T cell responses. Differential regulation of sPD-L1 during the early and late RA may indicate transposition from acute to chronic inflammation

Sensitization to molecular dog allergens in an adult population : Results from the West Sweden Asthma Study

Background: As the prevalence of dog allergy rises, component resolved diagnosis might improve the diagnosis, understanding of the clinical outcomes and the effectiveness of immunotherapy. Considering the paucity of data in adults, the current study characterized the patterns of sensitization to dog molecular allergens in an adult population. Methods: Data were derived from the West Sweden Asthma Study, a population-based and representative sample of adults from western Sweden. Of the 2006 subjects clinically examined, 313 participants sensitized to whole dog allergen extract were measured for specific immunoglobulin E (sIgE) levels to Can f 1, Can f 2, Can f 3, Can f 4, Can f 5 and Can f 6 using ImmunoCAP™. Polysensitization was defined as sensitization to ≥3 components. Overlapping sensitization was defined as having concomitant sensitization to at least two dog molecular allergen families (lipocalin, albumin or prostatic kallikrein). Results: Of 313, 218 (70%) subjects tested positive to at least one dog allergen component. Sensitization to Can f 1 (43%) was the most common, followed by Can f 5 (33%) among molecular allergens, while sensitization to lipocalins (56%) was the most common among component families. Polysensitization was found in 22% of all participants and was more common in participants with than in those without asthma. Subjects with asthma were less likely to be monosensitized to Can f 5 than those without asthma. Subjects with asthma had higher IgE levels of Can f 3, Can f 4 and Can f 6 than those without asthma. Overlapping sensitizations also differed between those with asthma and allergic rhinitis and those without. Conclusion: Increased knowledge about the sensitization patterns of dog allergen components can aid in defining their role in asthma and rhinitis. In complex clinical cases of dog allergy, a detailed analysis of dog allergen components can provide additional information on the nature of sensitization.publishedVersionPeer reviewe

Asthma in West Sweden - a translational study from epidemiology to proteomics

Asthma has been increasing in prevalence and morbidity, however it is unclear if the increase continues. Asthma has long been regarded as a single disease entity, but is now recognised as a heterogenic disease with different phenotypes. The overall aim was to investigate asthma and selected phenotypes in the population with regard to prevalence, medication use and differences in mechanism. In an epidemiologic study of 18 870 responders to a postal questionnaire, living in Gothenburg and Västra Götaland, the prevalence of physician-diagnosed asthma was 8.3%. Compared with a study conducted 18 years ago on the island of Hisingen, the prevalence of most respiratory symptoms had decreased, while there was a small increase in asthma prevalence and a significant increase in allergic rhinitis. As an epidemiological proxy to severe asthma, multi-symptom asthma (MSA) was defined from responses to the questionnaire. The prevalence of MSA was 2% in the population and 24% among asthmatics. The definition was verified in a subgroup of subjects invited to our research clinic. MSA was associated with signs of more severe disease, such as lower lung function, more airway inflammation, hyper-responsiveness and more severe health outcomes. Of subjects with MSA, 92% used asthma medication, compared with 61% of other asthmatic subjects. Inhaled corticosteroids were used by 70% of subjects with MSA, who also reported more frequent use of asthma medication. Selected participants from three phenotypes of asthma, and healthy controls were included in a proteomics study where several differences in protein expression patterns could be detected in nasal lavage fluid. In total 193 proteins was identified with a fold change of at least 1.3 as compared to healthy, these proteins represent different biological functions and pathways between phenotypes. We conclude that the previous increase in asthma prevalence has ceased and that respiratory symptoms are decreasing. MSA is common among asthmatics and is related to signs of more severe disease, hence MSA can be used an epidemiological marker of disease severity. Medication use is high in MSA, however under-treatment occurs. Further, quantitative proteomics on nasal lavage fluid can be used to identify differences in protein expression between asthma phenotypes, and possibly to detect differences in mechanism

Consider personality, medication adherence and asthma control in efforts to improve health-related quality of life in adult asthmatics!

Consider personality, medication adherence and asthma control in efforts to improve health-related quality of life in adult asthmatics! Authors: Axelsson Malin1, Ekerljung Linda2, Lundbäck Bo2 1Department of Care Science, Faculty of Health and Society, Malmö University, Malmö, Sweden 2Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Gothenburg, Sweden Introduction: Asthma is a common respiratory disease, which often requires regular medication treatment. In individuals with asthma, assessments of health-related quality of life (HRQL) serve as an essential health outcome as they capture personal perspectives and experiences of everyday life with asthma and the ongoing medication treatment. Personality, adherence to medication treatment and asthma control are important influential factors of HRQL in adult individuals with asthma. However, these factors have rarely been investigated together. Therefore, the aim was to elucidate associations between personality, adherence, asthma control and HRQL in adult asthmatics. Methods: Adult asthmatics (n=337) with prescribed regular asthma medication treatment selected from West Sweden Asthma Study, participated by completing questionnaires on personality, adherence to asthma medication treatment, asthma control and HRQL. Two path models with the personality traits Neuroticism and Conscientiousness as independent variables, HRQL as dependent variable and adherence and asthma control as mediators were tested. Results: In the first path model, Neuroticism was negatively associated with adherence to asthma medication treatment and the mediated effect of adherence on HRQL went through that of perceived asthma control. In the second path model, both adherence and perceived asthma control functioned as mediators between Conscientiousness and HRQL. In this model, the effect of adherence on HRQL also went through that of perceived asthma control. Conclusion: Improving adherence in adult asthmatics scoring higher on the personality trait Neuroticism or lower on the personality trait Conscientiousness would most likely have a positive impact on their perceived asthma control, which in turn would increase their HRQL. In efforts to improve HRQL in adult asthmatics, individual differences, adherence to asthma medication treatment and perceived asthma control need to be taken into consideratio

Boost self-efficacy for better health outcomes in adult asthmatics!

Boost self-efficacy for better health outcomes in adult asthmatics! Authors: Axelsson Malin1, Ekerljung Linda 2, Lundbäck Bo2 1Department of Care Science, Faculty of Health and Society, Malmö University, Malmö, Sweden 2Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Gothenburg, Sweden Introduction: Self- efficacy i.e. confidence in ability to handle challenges in everyday life could influence how individuals suffering from long-term disease such as asthma manage the disease, the medication treatment and symptoms, which in turn could influence both disease progression and health-related quality of life (HRQL). Aim: to explore the function of concerns with asthma medication and asthma control as mediators between self-efficacy and HRQL. Method: Adult asthmatics (n=479, 60% women) aged between 19 and 78 years selected from West Sweden Asthma Study completed questionnaires on self-efficacy, concerns with asthma medication, asthma control and HRQL. Two path models with self-efficacy as independent variable, mental and physical HRQL as dependent variables and concerns with asthma medication and asthma control as mediators were conducted. Results: In both path models, self-efficacy was negatively associated with concerns with asthma medication (β= -.130, p=0.005) and positively associated with asthma control (β =.100, p=0.027). In both path models, the effect of concerns with asthma medication on both mental and physical HRQL went through that of asthma control (β=-.138, p=0.003). Both concerns with asthma medication and asthma control mediated the effect of self-efficacy on both mental (β =.132, p=0.002) and physical HRQL (β =.455, p=0.001). Conclusion: Adult asthmatics with lower self-efficacy need support to strengthen their self-efficacy and assistance to overcome their concerns with the asthma medication in order to improve their asthma control. Better self-efficacy and reduced concerns with asthma medication will increase asthma control, which in turn most likely will have a positive effect on both mental and physical HRQL in adult asthmatics