Airways inflammation and treatment during acute exacerbations of COPD

INTRODUCTION: Inflammation is a core feature of acute chronic obstructive pulmonary disease (COPD) exacerbations. It is important to focus on inflammation since it gives insight into the pathological changes causing an exacerbation, thereby possibly providing directions for future therapies which modify inflammation. OBJECTIVES: To provide a cell-by-cell overview of the inflammatory processes during COPD exacerbations. To evaluate cell activation, and cytokine production, cellular interactions, damaging effects of inflammatory mediators to tissue, and the relation to symptoms at the onset of COPD exacerbations. To speculate on future therapeutic options to modify inflammation during COPD exacerbations. RESULTS: During COPD exacerbations, there is increased airway wall inflammation, with pathophysiological influx of eosinophils, neutrophils, and lymphocytes. Although links have been suggested between the increase in eosinophils and lymphocytes and a viral etiology of the exacerbation, and between the increase in neutrophils and a bacterial aetiology, these increases in both inflammatory cell types are not limited to the respective aetiologies and the underlying mechanisms remain elusive. CONCLUSION: Further research is required to fully understand the inflammatory mechanisms in the onset and development of COPD exacerbations. This might make inflammatory pathway-specific intervention possible, resulting in a more effective treatment of COPD exacerbations with fewer side effects

Bewoners profielen van duurzame wijken:huur- en koopmotieven van een duurzame woning inrelatie met de leefstijlen en de toepassing van duurzaamheid

In dit onderzoeksrapport staat de wijk de Drielanden te Groningen Centraal. Aan de noordoostzijde van de stad Groningen is de wijk gelegen. De wijk drielanden bestaat sinds 1995, in die tijd was het een vooruitstrevende wijk op het gebied van duurzaamheid. Tegenwoordig worden veel nieuwe duurzame wijken gebouwd, maar er is een terugloop geconstateerd in de koop van woningen in duurzame wijken. Met behulp van dit onderzoek wordt duidelijk hoe er in de toekomst op koop- en verkoopmotieven ingespeeld kan worden. Er gaat onderzocht worden wat de motieven zijn voor de koop van een duurzame woning, het gaat hier om bewuste, onbewuste en psychologische motieven. Dit leidt tot de volgende probleemstelling: Welke kenmerken van de bewoners uit de Drielanden hangen samen met de koopmotieven? Het vraagtype van de probleemstelling is definiëren. Het onderzoek is uitgevoerd met een enquête, dit is het meetinstrument. Het totale domein van dit onderzoek bedraagt 390 huishoudens verdeeld over de drie straten in de wijk Drielanden; Waterland met 166 huishoudens, Zonland met 142 huishoudens en Mooiland met 82 huishoudens. Het onderzoek is uitgevoerd om de verkoop- en koopmotieven in de duurzame wijk te onderzoeken, dit zijn de onderzoekseenheden van het onderzoek. De methode die gebruikt is voor het onderzoek is een combinatie van de kwantitatieve (desk research) en de kwalitatieve strategie (enquête). De doelstelling van het onderzoek is weten welke motieven kopers van 'duurzame woningen' hebben om een dergelijke woning te kopen, zodat de neergang in de verkoop en verhuur van duurzame woningen kan worden tegengegaan. De hoofdresultaten uit het onderzoek hebben betrekking op de leefstijlen, toepassing van duurzaamheid en de koop- en huurmotieven van de bewoners van de Drielanden. Er zijn vier leefstijlen te onderscheiden. Eén leefstijl is minder vertegenwoordigd, namelijk vitaliteit. Deze beslaat de bevolkingsgroep die ego georiënteerd en extravert is. De toepassing van duurzaamheid is gemiddeld matig tot licht voldoende. Voor een duurzame wijk is dit zeer beneden de maat. In verhouding tot de motieven is dit te verklaren aangezien ongeveer 1 op de 10 bewoners voor duurzaamheid heeft gekozen. De overige bewoners hebben andere redenen als ligging en een ruimere woning. Dit zijn direct de twee meest voorkomende motieven. Er zal ongetwijfeld samenhang zijn tussen duurzaamheid en een ruim opgezette wijk. Het ruimer wonen kan dus in verband staan met het motief duurzaam wonen. Dit zal een juist onderwerp zijn voor een eventueel vervolgonderzoek. Studentenonderzoek in het kader van het thema Duurzaam bouwe

Does calcium diffusional global feedback leads to slow light adaptation in Drosophila photoreceptors? - A 3D biophysical modelling approach

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Social norms in Korsakoff's syndrome and alcohol-related dementia

ObjectiveSocial cognition is essential for individuals to perceive, process, and interpret social information that enables them to function effectively in society. Korsakoff's syndrome (KS) and alcohol-related dementia (ARD) are alcohol-related cognitive disorders that are likely to impair social cognition. This study aimed to investigate the ability to judge social norms in KS and ARD in comparison to healthy subjects.MethodThe study included 30 patients with KS, 10 patients with ARD, and 74 age-, sex-, and education-matched control participants. The Social Norms Questionnaire - Dutch version (SNQ-NL) was used to measure social cognition, and standardized tests were used to examine the association between social cognition and executive functioning.ResultsBoth KS and ARD patients performed worse in judging social norms when compared to healthy controls, but there was no significant difference between KS and ARD. Both KS and ARD patients performed worse on the SNQ-NL, judging appropriate behavior as inappropriate (Overadhere errors), than controls. When compared to control participants, patients with KS demonstrated significantly more Break Errors, while the differences between the ARD group and the control group did not reach statistical significance. There were no significant correlations between the SNQ-NL variables and performances on standardized tests for executive functioning in both the KS and control group.ConclusionsThis study aimed to investigate the ability to judge social norms in KS and ARD in comparison to healthy subjects. The results show that compared to a control group, both KS and ARD patients performed worse in judging social norms. KS and ARD patients scored equally low on social norms identification. Overall, these findings can further help us understand the difficulties in social behavior as experienced by patients and care staff, since problems in accurately judging social norms could possibly contribute to the severe behavioral issues as observed in alcohol-related disorders

Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression

Many workers are daily exposed to occupational agents like gases/fumes, mineral dust or biological dust, which could induce adverse health effects. Epigenetic mechanisms, such as DNA methylation, have been suggested to play a role. We therefore aimed to identify differentially methylated regions (DMRs) upon occupational exposures in never-smokers and investigated if these DMRs associated with gene expression levels. To determine the effects of occupational exposures independent of smoking, 903 never-smokers of the LifeLines cohort study were included. We performed three genome-wide methylation analyses (Illumina 450 K), one per occupational exposure being gases/fumes, mineral dust and biological dust, using robust linear regression adjusted for appropriate confounders. DMRs were identified using comb-p in Python. Results were validated in the Rotterdam Study (233 never-smokers) and methylation-expression associations were assessed using Biobank-based Integrative Omics Study data (n = 2802). Of the total 21 significant DMRs, 14 DMRs were associated with gases/fumes and 7 with mineral dust. Three of these DMRs were associated with both exposures (RPLP1 and LINC02169 (2x)) and 11 DMRs were located within transcript start sites of gene expression regulating genes. We replicated two DMRs with gases/fumes (VTRNA2-1 and GNAS) and one with mineral dust (CCDC144NL). In addition, nine gases/fumes DMRs and six mineral dust DMRs significantly associated with gene expression levels. Our data suggest that occupational exposures may induce differential methylation of gene expression regulating genes and thereby may induce adverse health effects. Given the millions of workers that are exposed daily to occupational exposures, further studies on this epigenetic mechanism and health outcomes are warranted

Health and lifespan of Swiss men born in an alpine region in 1905–1907

Body height and body mass index (BMI) are associated with later life outcomes in present and historical populations. We examine the case study of the Swiss Alpine canton of Glarus, which was highly industrialised at the beginning of the 20th century. Our study links conscription registers to genealogical registers at the individual level in Switzerland for the first time. We analyse whether body height, BMI, socioeconomic position (HISCLASS), region of residence, fitness to serve (as a proxy for health status in a military context), and goitre status (as a proxy for iodine deficiency) in young adulthood are associated with lifespan. We transcribed conscription records of 1073 men born between 1905 and 1907 and recruited between 1925 and 1927 (coverage birth cohorts 96%). Of the 827 young men residing within the canton, we were able to identify 635 (76.8%) in the cantonal genealogical register. Using body height, chest circumference, and upper arm circumference, we estimated BMI. We find socioeconomic differences for height and estimated BMI at conscription age. Young men with a recorded goitre were taller. We also present a positive association between body height and lifespan, with small men being particularly disadvantaged. In a small subsample of two municipalities, we estimated the heritability of height to be 65%

Measuring patients' judgements on the quality of long-term Korsakoff care they receive:the development of the Korsakoff Consumer Quality Index (KCQI)

Background: Korsakoff's syndrome (KS) is a severe neuropsychiatric disorder resulting from chronic alcoholism and thiamine deficiency, characterized by severe anterograde amnesia and central executive deficits. Patients with KS require specialized long-term care due to the complex interaction of cognitive, neuropsychiatric, and somatic issues. Despite the unique needs of KS patients, there is a lack of standardized instruments to assess their perspectives on the quality of care. Aim: This paper presents the development of the Korsakoff Consumer Quality Index (KCQI), a self-report screening instrument for client satisfaction in long-term KS care.Methods: To establish the psychometric properties of the KCQI, two studies were conducted to assess its reliability and validity. In the first study psychometric properties of the KCQI were investigated by means of a reliability assessment and an exploratory factor analysis in 75 long-term inpatients diagnosed with KS. In the second study, a confirmatory factor analysis was carried out to establish the factor structure of the instrument in a new group of 92 KS patients.Results: The resulting 14-item KCQI had a factor structure with three factors: ‘Autonomy and Connectedness’, ‘Influence on Care’ and ‘Activity Level’. Model fit was sufficient, with a good reliability. Conclusions: The results indicate that the KCQI is an internally valid and reliable instrument that can be interpreted using a three-factor structure, and contribute to the understanding of KS patient perspectives on care quality.</p

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

The long-lasting legacy of reproduction:lifetime reproductive success shapes expected genetic contributions of humans after ten generations

An individual’s lifetime reproductive success (LRS) measures its realised genetic contributions to the next generation, but how well does it predict these over longer periods? Here we use human genealogical data to estimate expected individual genetic contributions (IGC) and quantify the degree to which LRS, relative to other fitness proxies, predicts IGC over longer periods in natural populations. This allows an identification of the life-history stages that are most important in shaping variation in IGC. We use historical genealogical data from two non-isolated local populations in Switzerland to estimate the stabilised IGC for 2,230 individuals ~10 generations after they were born. We find that LRS explains 30% less variation in IGC than the best predictor of IGC, the number of grandoffspring. However, albeit less precise than the number of grandoffspring, we show that LRS does provide an unbiased prediction of IGC and overall predicts IGC better than lifespan and similarly when accounting for offspring survival to adulthood. Overall, our findings demonstrate the value of human genealogy data to evolutionary biology and showing that reproduction - more than lifespan or offspring survival - impacts the long-term genetic contributions of historic humans, even in a population with appreciable migration