Characteristics and health burden of the undiagnosed population at risk of chronic obstructive pulmonary disease in China

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality in China. However, identifying patients has proved challenging, resulting in widespread under-diagnosis of the condition. We examined the prevalence of COPD diagnosis and COPD risk among adults in urban mainland China, the factors associated with having a COPD diagnosis or COPD risk, and the healthcare resource use and health outcomes of these groups compared with controls. METHODS: Respondents to the 2017 National Health and Wellness Survey in China (n = 19,994) were classified into three groups: 'COPD Diagnosed', 'COPD Risk (undiagnosed)', and Control (unaffected), based on their self-reported diagnosis and Lung Function Questionnaire (LFQ) score. The groups were characterised by sociodemographic, health-related quality of life (HRQoL), productivity impairment, and healthcare resource use. Pairwise comparisons (t tests and chi-squared tests) and multivariable regression analyses were used to investigate factors associated with being at risk of, or diagnosed with, COPD. RESULTS: 3320 (16.6%) respondents had a suspected risk of COPD but did not report receiving a diagnosis. This was projected to 105.3 million people, or 16.9% of adult urban Chinese. Of these respondents with an identified risk, only 554 (16.7%) were aware of COPD by name. Relative to those without COPD, those with a risk of COPD (undiagnosed) had significantly greater healthcare resource use, lower productivity and lower HRQoL not only compared to those without COPD, but also compared to people with a COPD diagnosis. Factors associated with increased odds of being at risk of COPD were older age, smoking, alcohol consumption, overweight BMI, occasional exercise, higher comorbidities, asthma diagnosis, being female, lower education, not being employed, and living in a high pollution province (p < 0.05). CONCLUSIONS: There is a substantial group of individuals, undiagnosed, but living with a risk of COPD, who have impaired HRQoL, lower productivity and elevated healthcare resource use patterns. Case-detection tools such as the LFQ may prove a quick and cost-effective approach for identifying these at-risk individuals for further definitive testing and appropriate treatment in China

Spider-silk inspired polymeric networks by harnessing the mechanical potential of β-sheets through network guided assembly.

The high toughness of natural spider-silk is attributed to their unique β-sheet secondary structures. However, the preparation of mechanically strong β-sheet rich materials remains a significant challenge due to challenges involved in processing the polymers/proteins, and managing the assembly of the hydrophobic residues. Inspired by spider-silk, our approach effectively utilizes the superior mechanical toughness and stability afforded by localised β-sheet domains within an amorphous network. Using a grafting-from polymerisation approach within an amorphous hydrophilic network allows for spatially controlled growth of poly(valine) and poly(valine-r-glycine) as β-sheet forming polypeptides via N-carboxyanhydride ring opening polymerisation. The resulting continuous β-sheet nanocrystal network exhibits improved compressive strength and stiffness over the initial network lacking β-sheets of up to 30 MPa (300 times greater than the initial network) and 6 MPa (100 times greater than the initial network) respectively. The network demonstrates improved resistance to strong acid, base and protein denaturants over 28 days

New Approaches towards the Design of Tough Amphiphilic Polymeric Co-networks

© The Royal Society of Chemistry 2020. Since the 1960s, polymer network hydrogels have been used for various applications. However, these applications have been restricted to non-load-bearing ones, due to the inherent mechanical weakness of common hydrogels. This weakness is attributed to the irregular crosslinking density, the high proportion of singly-attached (dangling and, therefore, elastically inactive) chains and the broadly varying distance between crosslinking points. In recent years, ground-breaking studies focusing on the development of novel approaches to fabricate near-ideal polymer network hydrogels with excellent mechanical properties have been developed. In this chapter, these new approaches will be outlined, with specific interest in amphiphilic polymer co-networks (APCNs), i.e. networks containing both hydrophilic and hydrophobic domains. The ability to generate these near-ideal networks, which often also possess 'smart' stimuli-responsive properties, would allow APCNs to be used in a wide range of advanced applications, including soft robotics, biomaterials and materials science. These new synthetic methodologies will be described in this chapter and will be separated into either fundamentally altering the network architecture and/or by employing facile and orthogonal coupling chemistries

Fragile charge order in the nonsuperconducting ground state of the underdoped high-temperature superconductors.

The normal state in the hole underdoped copper oxide superconductors has proven to be a source of mystery for decades. The measurement of a small Fermi surface by quantum oscillations on suppression of superconductivity by high applied magnetic fields, together with complementary spectroscopic measurements in the hole underdoped copper oxide superconductors, point to a nodal electron pocket from charge order in YBa2Cu3(6+δ). Here, we report quantum oscillation measurements in the closely related stoichiometric material YBa2Cu4O8, which reveals similar Fermi surface properties to YBa2Cu3(6+δ), despite the nonobservation of charge order signatures in the same spectroscopic techniques, such as X-ray diffraction, that revealed signatures of charge order in YBa2Cu3(6+δ). Fermi surface reconstruction in YBa2Cu4O8 is suggested to occur from magnetic field enhancement of charge order that is rendered fragile in zero magnetic fields because of its potential unconventional nature and/or its occurrence as a subsidiary to more robust underlying electronic correlations.B.T., A.S, and S.E.S. acknowledge support from the Royal Society, the Winton Programme for the Physics of Sustainability, and the European Research Council under the European Unions Seventh Framework Programme (grant number FP/2007-2013)/ ERC Grant Agreement number 337425. N.H., Z.Z., F.F.B., and B.J.R. acknowl- edge support for high-magnetic-field experiments from the US Department of Energy, Office of Science, BES- MSE `Science of 100 Tesla' programme. G.G.L. acknowl- edges support from EPSRC grant EP/K012894/1. Work at NIU was supported by The Institute for Nanoscience, Engineering, and Technology - InSET. A portion of this work was performed at the National High Magnetic Field Laboratory, which is supported by NSF co-operative agreement number DMR-0654118, the state of Florida, and the DOE. We are grateful for the experimental assis- tance provided by National High Magnetic Field Labora- tory personnel, including J. B. Betts, Y. Coulter, M. Gor- don, C. H. Mielke, A. Parish, R. McDonald, D. Rickel, and D. Roybal.This is the author accepted manuscript. The final version is available from the National Academy of Sciences via http://dx.doi.org/10.1073/pnas.150416411

Polyrotaxane-based thin film composite membranes for enhanced nanofiltration performance

© 2020 An urgent need exists for the development of advanced water purification technologies to meet the increasing global demand being placed on freshwater resources. Membrane-based separation technologies for size-selective contaminant removal represent a promising approach to achieve this goal. Here, a novel thin film composite nanofiltration membrane is prepared via interfacial polymerization of α-cyclodextrin on a commercially available polyacrylonitrile substrate. Subsequent in-situ inclusion complexation of alkyne-functionalized poly(ethylene glycol) (PEG) is then used to tune the polyrotaxane-based pores for size-dependent filtration. The resultant membrane shows excellent size-selective rejection rates for organic dye (e.g. rhodamine B, >99%) as well as heavy-metal ions (e.g. Co(II), >90%), while crucially maintaining high water permeance (e.g. H2O: 7.1 L h−1 m−2 bar−1). The facile and straightforward synthetic approach to the fabrication of polyrotaxane nanofiltration membranes, combined with their strong nanofiltration separation performance, holds significant promise for membrane-based water purification applications

Fgfr3 Is a Transcriptional Target of Ap2δ and Ash2l-Containing Histone Methyltransferase Complexes

Polycomb (PcG) and trithorax (trxG) proteins play important roles in establishing lineage-specific genetic programs through induction of chromatin modifications that lead to gene silencing or activation. Previously, we described an association between the MLL/SET1 complexes and a highly restricted, gene-specific DNA-binding protein Ap2δ that is required for recruitment of the MLL/SET1 complex to target Hoxc8 specifically. Here, we reduced levels of Ap2δ and Ash2l in the neuroblastoma cell line, Neuro2A, and analyzed their gene expression profiles using whole-genome mouse cDNA microarrays. This analysis yielded 42 genes that are potentially co-regulated by Ap2δ and Ash2l, and we have identified evolutionarily conserved Ap2-binding sites in 20 of them. To determine whether some of these were direct targets of the Ap2δ-Ash2l complex, we analyzed several promoters for the presence of Ap2δ and Ash2l by chromatin immunoprecipitation (ChIP). Among the targets we screened, we identified Fgfr3 as a direct transcriptional target of the Ap2δ-Ash2l complex. Additionally, we found that Ap2δ is necessary for the recruitment of Ash2l-containing complexes to this promoter and that this recruitment leads to trimethylation of lysine 4 of histone H3 (H3K4me3). Thus, we have identified several candidate targets of complexes containing Ap2δ and Ash2l that can be used to further elucidate their roles during development and showed that Fgfr3 is a novel direct target of these complexes

Microdevices for extensional rheometry of low viscosity elastic liquids : a review

Extensional flows and the underlying stability/instability mechanisms are of extreme relevance to the efficient operation of inkjet printing, coating processes and drug delivery systems, as well as for the generation of micro droplets. The development of an extensional rheometer to characterize the extensional properties of low viscosity fluids has therefore stimulated great interest of researchers, particularly in the last decade. Microfluidics has proven to be an extraordinary working platform and different configurations of potential extensional microrheometers have been proposed. In this review, we present an overview of several successful designs, together with a critical assessment of their capabilities and limitations

H2FPEF score predicts atherosclerosis presence in patients with systemic connective tissue disease

Background: Cardiovascular diseases are common cause of morbidity and mortality in patients with systemic connective tissue diseases (SCTD) due to accelerated atherosclerosis which couldn't be explained by traditional risk factors (CVDRF). Hypothesis: We hypothesized that recently developed score predicting probability of heart failure with preserved ejection fraction (H2FPEF), as well as a measure of right ventricular-pulmonary vasculature coupling [tricuspid annular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) ratio], are predictive of atherosclerosis in SCTD. Methods: 203 patients (178 females) diagnosed with SCTD underwent standard and stress-echocardiography (SE) with TAPSE/PASP and left ventricular (LV) diastolic filling pressure (E/e') measurements, carotid ultrasound and computed tomographic coronary angiography. Patients who were SE positive for ischemia underwent coronary angiography (34/203). The H2FPEF score was calculated according to age, body mass index, presence of atrial fibrillation, ≥2 antihypertensives, E/e' and PASP. Results: Mean LV ejection fraction was 66.3 ± 7.1%. Atherosclerosis was present in 150/203 patients according to: 1) intima-media thickness>0.9 mm; and 2) Agatstone score > 300 or Syntax score ≥ 1. On binary logistic regression analysis, including CVDRF prevalence, echocardiographic parameters and H2FPEF score, only H2FPEF score remained significant for the prediction of atherosclerosis presence (χ2 = 19.3, HR 2.6, CI 1.5-4.3, p < 0.001), and resting TAPSE/PASP for the prediction of a SE positive for ischemia (χ2 = 10.4, HR 0.01, CI = 0.01-0.22, p = 0.004). On ROC analysis, the optimal threshold value for identifying patients with atherosclerosis was a H2FPEF score ≥2 (Sn 60.4%, Sp 69.4%, area 0.67, SE = 0.05, p < 0.001). Conclusions: H2FPEF score and resting TAPSE/PASP demonstrated clinical value for an atherosclerosis diagnosis in patients diagnosed with SCTD

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology. The human family includes 19 members that can be sub-grouped on the basis of their known substrates, namely the aggrecanases or proteoglycanases (ADAMTS1, 4, 5, 8, 9, 15 and 20), the procollagen N-propeptidases (ADAMTS2, 3 and 14), the cartilage oligomeric matrix protein-cleaving enzymes (ADAMTS7 and 12), the von-Willebrand Factor proteinase (ADAMTS13) and a group of orphan enzymes (ADAMTS6, 10, 16, 17, 18 and 19). Control of the structure and function of the extracellular matrix (ECM) is a central theme of the biology of the ADAMTS, as exemplified by the actions of the procollagen-N-propeptidases in collagen fibril assembly and of the aggrecanases in the cleavage or modification of ECM proteoglycans. Defects in certain family members give rise to inherited genetic disorders, while the aberrant expression or function of others is associated with arthritis, cancer and cardiovascular disease. In particular, ADAMTS4 and 5 have emerged as therapeutic targets in arthritis. Multiple ADAMTSs from different sub-groupings exert either positive or negative effects on tumorigenesis and metastasis, with both metalloproteinase-dependent and -independent actions known to occur. The basic ADAMTS structure comprises a metalloproteinase catalytic domain and a carboxy-terminal ancillary domain, the latter determining substrate specificity and the localization of the protease and its interaction partners; ancillary domains probably also have independent biological functions. Focusing primarily on the aggrecanases and proteoglycanases, this review provides a perspective on the evolution of the ADAMTS family, their links with developmental and disease mechanisms, and key questions for the future