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of bias, imprecision and indirectness found across included studies. Future, high quality longitudinal cohort studies are required to investigate the predictive value of baseline psychological factors on long-term clinical outcome.

The overall body of the evidence after applying the GRADE criteria was low to very low certainty evidence, due to risk of bias, imprecision and indirectness found across included studies. Future, high quality longitudinal cohort studies are required to investigate the predictive value of baseline psychological factors on long-term clinical outcome.

The ageing population in most low-and middle-income countries is accompanied by an increased risk of non-communicable diseases culminating in a poor quality of life (QOL). However, the factors accelerating this poor QOL have not been fully examined in Nepal. Therefore, this study examined the factors associated with the QOL of older adults residing in the rural setting of Nepal.

Data from a previous cross-sectional study conducted among older adults between January and April 2018 in in rural Nepal was used in this study. The analytical sample included 794 older adults aged ≥60 years, selected by a multi-stage cluster sampling approach. QOL was measured using the Older People’s Quality of Life tool; dichotomized as poor and good QOL. Other measures used included age, gender, ethnicity, religion, marital status, physical activity, and chronic diseases such as osteoarthritis, cardiovascular disease, diabetes, chronic obstructive pulmonary disease (COPD), and depression. The factors associated with QOL were egrams aimed at addressing the identified biosocial and disease conditions that catalyse poor QOL in this older population residing in rural parts of Nepal.

The findings of this study reinforce the need of improving QOL of older adults through implementing programs aimed at addressing the identified biosocial and disease conditions that catalyse poor QOL in this older population residing in rural parts of Nepal.[This corrects the article DOI 10.1371/journal.pone.0176139.].Genome wide association studies (GWAS) have identified several genomic loci with candidate modifiers of cystic fibrosis (CF) lung disease, but only a small proportion of the expected genetic contribution is accounted for at these loci. We leveraged expression data from CF cohorts, and Genotype-Tissue Expression (GTEx) reference data sets from multiple human tissues to generate predictive models, which were used to impute transcriptional regulation from genetic variance in our GWAS population. The imputed gene expression was tested for association with CF lung disease severity. By comparing and combining results from alternative approaches, we identified 379 candidate modifier genes. We delved into 52 modifier candidates that showed consensus between approaches, and 28 of them were near known GWAS loci. A number of these genes are implicated in the pathophysiology of CF lung disease (e.g., immunity, infection, inflammation, HLA pathways, glycosylation, and mucociliary clearance) and the CFTR protein biology (e.g., cytoskeleton, microtubule, mitochondrial function, lipid metabolism, endoplasmic reticulum/Golgi, and ubiquitination). Gene set enrichment results are consistent with current knowledge of CF lung disease pathogenesis. selleck chemicals HLA Class II genes on chr6, and CEP72, EXOC3, and TPPP near the GWAS peak on chr5 are most consistently associated with CF lung disease severity across the tissues tested. The results help to prioritize genes in the GWAS regions, predict direction of gene expression regulation, and identify new candidate modifiers throughout the genome for potential therapeutic development.

Sub-epithelial fibrosis is a characteristic feature of airway remodeling in asthma which correlates with disease severity. Current asthma medications are ineffective in treating fibrosis. In this study, we aimed to investigate the mitochondrial phenotype in fibroblasts isolated from airway biopsies of non-asthmatic and severe asthmatic subjects by examining mitophagy as a mechanism contributing to fibroblast persistence and thereby, fibrosis in severe asthma.

Bioinformatics analysis of publicly available transcriptomic data was performed to identify the top enriched pathways in asthmatic fibroblasts. Endogenous expression of mitophagy markers in severe asthmatic and non-asthmatic fibroblasts was determined using qRT-PCR, western blot and immunofluorescence. Mitophagy flux was examined by using lysosomal protease inhibitors, E64d and pepstatin A. Mitochondrial membrane potential and metabolic activity were also evaluated using JC-1 assay and MTT assay, respectively.

Bioinformatics analysis revealed the edria may contribute to fibrosis in severe asthma by promoting the persistence and pro-fibrotic phenotype of fibroblasts.

Our results demonstrated a role for mitophagy in the pathogenesis of severe asthma where the enhanced turnover of damaged mitochondria may contribute to fibrosis in severe asthma by promoting the persistence and pro-fibrotic phenotype of fibroblasts.As the capital and one of the metropolises in China, Beijing has met with a number of serious so-called “urban diseases” in the process of rapid urbanization such as blind expansion of urban areas, explosion of population and the increase of urban heat island effect. To treat these “urban diseases” and make the metropolis develop healthful and sustainable in Beijing in the future, the spatial characteristics of metropolis developments in Beijing are explored in this paper. The urban built-up areas in Beijing are extracted using the DMSP-OLS nighttime light data from 1992 to 2013. The characteristics of the urban developments of Beijing are studied, including spatial and temporal scales of urban developments, urban barycenter of Beijing and its transfer trajectory, variations of urban spatial forms and the differences of urban internal developments. The results have shown that the built-up areas had been increasing and circling extending from the central urban areas to the outer spaces in the last 21 years. The built-up area had expanded by 878km2 in 1992-2013, and the built-up area in 2013 had expanded to three times comparing to that of 1992. The expanding area of the built-up area in the northeast is the largest. The expansion of the urban had mainly occurred in 1996-2007, and the expanded area had accounted for 92% of the total research period. During the whole research period, the urban barycenter of Beijing had moved 5000.71 meters towards Northeast 28° of its original place from Dongcheng District to Chaoyang District. The development level of each municipal district had been increasing year by year, and the development differences among the municipal districts had been gradually reduced; the spatial forms of Beijing had been alternately changed between extensive and intensive expansion. The results of this study can help to plan urban land use and people migration of Beijing.