Fatigue and health-related quality of life among patients with chronic obstructive pulmonary disease in China.

OBJECTIVES: Fatigue is an important yet ignored symptom of chronic obstructive pulmonary disease (COPD). However, there is a paucity of literature from China on fatigue and its association with health-related quality of life (HRQoL) among COPD patients. The purpose of this study was to (a) evaluate fatigue of COPD inpatients in China and (b) explore the association between fatigue and HRQoL. METHODS: This cross-sectional study recruited patients hospitalised for an acute exacerbation of COPD within one month from three general hospitals in central China. Disease severity, fatigue and HRQoL were assessed for all participants using COPD Assessment Test (CAT), 9-item Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-F) and 12-Item Short-Form Health Survey (SF-12v2). RESULTS: A total of 210 COPD patients participated in the study between April 2017 and January 2018, with an average age of 71.1 ± 12.2 years old. The overall prevalence of moderate to severe fatigue was 48.5%. A worse FACIT-F score was associated with worse CAT score (r = -0.74, P < 0.01; B = -0.70, P < 0.01) and worse SF-12v2 score (r = 0.77, P < 0.01; B = 0.66, P < 0.01). CONCLUSION: Almost half of the COPD patients experience moderate to severe fatigue. Patients with greater disease severity exhibited more severe fatigue and worse HRQoL. Fatigue symptom has a strongly negative effect on COPD patients' HRQoL, physical health and mental health. Health personnel is recommended to provide fatigue-related screening, counselling and health education, particularly for patients with moderate to severe COPD.

Efflux of monoclonal antibodies from rat brain by neonatal Fc receptor, FcRn.

Monoclonal antibody (mAb) engineering that optimizes binding to receptors present on brain vascular endothelial cells has enabled them to cross through the blood-brain barrier (BBB) and access the brain parenchyma to treat neurological diseases. However, once in the brain the extent to which receptor-mediated reverse transcytosis clears mAb from the brain is unknown. The aim of this study was to determine the contribution of the neonatal Fc-receptor (FcRn) in rat brain efflux employing two different in vivo drug delivery models. Two mAb variants with substantially different affinities to FcRn, and no known neuronal targets, (IgG1 N434A and H435A) were administered to rats via intranasal-to-central nervous system (CNS) and intra-cranial dosing techniques. Levels of full-length IgG were quantified in serum and brain hemispheres by a sensitive enzyme-linked immunosorbent assay (ELISA). Following intra-nasal delivery, low cerebral hemisphere levels of variants were obtained at 20min, with a trend towards faster clearance of the high FcRn binder (N434A); however, the relatively higher serum levels confounded analysis of brain FcRn contribution to efflux. Using stereotaxic coordinates, we optimized the timing and dosing regimen for injection of mAb into the cortex. Levels of N434A, but not H435A, decreased in the cerebral hemispheres following bilateral injection into the rat cortex and higher levels of N434A were detected in serum compared to H435A after 24h. Immunohistochemical staining of human IgG1 in sections of cortex was consistent with these results, illustrating relatively less intense immunostaining in N434A than H435A dosed animals. Using two in vivo methods with direct cranial administration, we conclude that FcRn plays an important role in efflux of IgG from the rat brain.

Taxonomic utility of a phylogenetic analysis of phosphoglycerate kinase proteins of Archaea, Bacteria, and Eukaryota: insights by Bayesian analyses.

We studied 131 protein sequences of the essentially ubiquitous glycolytic enzyme 3-phosphoglycerate kinase (3-PGK) by Bayesian analyses in three Domains: 15 Archaea, 83 Bacteria, and 33 Eukaryota. The posterior distribution of phylogenetic trees developed were based on a uniform prior, the WAG model of protein evolution, Metropolis-Hastings sampling in a Markov chain Monte Carlo analysis, and a package of diagnostics to critically evaluate the validity of the analyses. The 15 Archaea separated with high posterior probability. The archaean Phyla Euryarchaeota and the apparently Euryarchaeota derived Crenarchaeota were monophyletic. The 33 Eukaryota separated into two main groups: the non-chlorophyllous forms with coherent sub-groupings of Euglenozoa, Alveolata, Fungi, and Metazoa and all the chlorophyllous species studied: the Plantae (Viridaeplantae), chlorophyllous Stramenopiles, and the chlorophyllous Bacteria. This association supports other opinions concerning the related lineage of cyanobacteria and the Plantae. The 3-PGK sequences from 83 Bacteria in almost every instance associated by their recognized taxal group: alpha-, beta-, gamma-, epsilon-proteobacteria, Chlamydia, Actinobacteridae, and Firmicutes. Firmicutes sequences were subdivided into three apparently monophyletic groups: the anaerobic Clostridia, the spore-forming Bacillales and a group containing the Mollicutes, Lactobacillales and non-spore-forming Bacillales. The 3-PGK-gene tree assemblage was notable both for its pervasive clustering in three Domains according to recognized taxonomic groupings of Class, Order, Family, and Genus. The 3-PGK enzyme or 3-PGK-like activity may have played a central role in the metabolism of the Universal Ancestor.