Hypoxia increases neutrophil-driven matrix destruction after exposure to Mycobacterium tuberculosis.

The importance of neutrophils in the pathology of tuberculosis (TB) has been recently established. We demonstrated that TB lesions in man are hypoxic, but how neutrophils in hypoxia influence lung tissue damage is unknown. We investigated the effect of hypoxia on neutrophil-derived enzymes and tissue destruction in TB. Human neutrophils were stimulated with M. tuberculosis (M.tb) or conditioned media from M.tb-infected monocytes (CoMTB). Neutrophil matrix metalloproteinase-8/-9 and elastase secretion were analysed by luminex array and gelatin zymography, gene expression by qPCR and cell viability by flow cytometry. Matrix destruction was investigated by confocal microscopy and functional assays and neutrophil extracellular traps (NETs) by fluorescence assay. In hypoxia, neutrophil MMP-8 secretion and gene expression were up-regulated by CoMTB. MMP-9 activity and neutrophil elastase (NE) secretion were also increased in hypoxia. Hypoxia inhibited NET formation and both neutrophil apoptosis and necrosis after direct stimulation by M.tb. Hypoxia increased TB-dependent neutrophil-mediated matrix destruction of Type I collagen, gelatin and elastin, the main structural proteins of the human lung. Dimethyloxalylglycin (DMOG), which stabilizes hypoxia-inducible factor-1α, increased neutrophil MMP-8 and -9 secretion. Hypoxia in our cellular model of TB up-regulated pathways that increase neutrophil secretion of MMPs that are implicated in matrix destruction

Age is a predicting factor for the association between CagA positive Helicobacter pylori (Hp) infection and serum pepsinogen I:II ratio in a high gastric cancer risk region in China

published_or_final_versio

Technical Design Report for the PANDA Solenoid and Dipole Spectrometer Magnets

This document is the Technical Design Report covering the two large spectrometer magnets of the PANDA detector set-up. It shows the conceptual design of the magnets and their anticipated performance. It precedes the tender and procurement of the magnets and, hence, is subject to possible modifications arising during this process.Comment: 10 pages, 14MB, accepted by FAIR STI in May 2009, editors: Inti Lehmann (chair), Andrea Bersani, Yuri Lobanov, Jost Luehning, Jerzy Smyrski, Technical Coordiantor: Lars Schmitt, Bernd Lewandowski (deputy), Spokespersons: Ulrich Wiedner, Paola Gianotti (deputy

Are C-Reactive Protein Associated Genetic Variants Associated with Serum Levels and Retinal Markers of Microvascular Pathology in Asian Populations from Singapore?

Introduction:C-reactive protein (CRP) levels are associated with cardiovascular disease and systemic inflammation. We assessed whether CRP-associated loci were associated with serum CRP and retinal markers of microvascular disease, in Asian populations.Methods:Genome-wide association analysis (GWAS) for serum CRP was performed in East-Asian Chinese (N = 2,434) and Malays (N = 2,542) and South-Asian Indians (N = 2,538) from Singapore. Leveraging on GWAS data, we assessed, in silico, association levels among the Singaporean datasets for 22 recently identified CRP-associated loci. At loci where directional inconsistencies were observed, quantification of inter-ethnic linkage disequilibrium (LD) difference was determined. Next, we assessed association for a variant at CRP and retinal vessel traits [central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE)] in a total of 24,132 subjects of East-Asian, South-Asian and European ancestry.Results:Serum CRP was associated with SNPs in/near APOE, CRP, HNF1A and LEPR (p-values ≤4.7×10-8) after meta-analysis of Singaporean populations. Using a candidate-SNP approach, we further replicated SNPs at 4 additional loci that had been recently identified to be associated with serum CRP (IL6R, GCKR, IL6 and IL1F10) (p-values ≤0.009), in the Singaporean datasets. SNPs from these 8 loci explained 4.05% of variance in serum CRP. Two SNPs (rs2847281 and rs6901250) were detected to be significant (p-value ≤0.036) but with opposite effect directions in the Singaporean populations as compared to original European studies. At these loci we did not detect significant inter-population LD differences. We further did not observe a significant association between CRP variant and CRVE or CRAE levels after meta-analysis of all Singaporean and European datasets (p-value >0.058).Conclusions:Common variants associated with serum CRP, first detected in primarily European studies, are also associated with CRP levels in East-Asian and South-Asian populations. We did not find a causal link between CRP and retinal measures of microvascular disease

Statin Prescription Patterns and Associations with Subclinical Inflammation

Background and Objectives: Statins have been extensively utilised in atherosclerotic cardiovascular disease (ASCVD) prevention and can inhibit inflammation. However, the association between statin therapy, subclinical inflammation and associated health outcomes is poorly understood in the primary care setting. Materials and Methods: Primary care electronic health record (EHR) data from the electronic Practice-Based Research Network (ePBRN) from 2012–2019 was used to assess statin usage and adherence in South-Western Sydney (SWS), Australia. Independent determinants of elevated C-reactive protein (CRP) were determined. The relationship between baseline CRP levels and hospitalisation rates at 12 months was investigated. Results: The prevalence of lipid-lowering medications was 14.0% in all adults and 44.6% in the elderly (≥65 years). The prevalence increased from 2012 to 2019 despite a drop in statin use between 2013–2015. A total of 55% of individuals had good adherence (>80%). Hydrophilic statin use and higher intensity statin therapy were associated with elevated CRP levels. However, elevated CRP levels were not associated with all-cause or ASCVD hospitalisations after adjusting for confounders. Conclusions: The prevalence and adherence patterns associated with lipid-lowering medications highlighted the elevated ASCVD-related burden in the SWS population, especially when compared with the Australian general population. Patients in SWS may benefit from enhanced screening protocols, targeted health literacy and promotion campaigns, and timely incorporation of evidence into ASCVD clinical guidelines. This study, which used EHR data, did not support the use of CRP as an independent marker of future short-term hospitalisations

An argument against the focus on Community Resilience in Public Health

Background - It has been suggested that Public Health professionals focus on community resilience in tackling chronic problems, such as poverty and deprivation; is this approach useful? Discussion - Resilience is always i) of something ii) to something iii) to an endpoint, as in i) a rubber ball, ii) to a blunt force, iii) to its original shape. “Community resilience” might be: of a neighbourhood, to a flu pandemic, with the endpoint, to return to normality. In these two examples, the endpoint is as-you-were. This is unsuitable for some examples of resilience. A child that is resilient to an abusive upbringing has an endpoint of living a happy life despite that upbringing: this is an as-you-should-be endpoint. Similarly, a chronically deprived community cannot have the endpoint of returning to chronic deprivation: so what is its endpoint? Roughly, it is an as-you-should-be endpoint: to provide an environment for inhabitants to live well. Thus resilient communities will be those that do this in the face of challenges. How can they be identified? One method uses statistical outliers, neighbourhoods that do better than would be expected on a range of outcomes given a range of stressors. This method tells us that a neighbourhood is resilient but not why it is. In response, a number of researchers have attributed characteristics to resilient communities; however, these generally fail to distinguish characteristics of a good community from those of a resilient one. Making this distinction is difficult and we have not seen it successfully done; more importantly, it is arguably unnecessary. There already exist approaches in Public Health to assessing and developing communities faced with chronic problems, typically tied to notions such as Social Capital. Communityresilience to chronic problems, if it makes sense at all, is likely to be a property that emerges from the various assets in a community such as human capital, built capital and natural capital. Summary - Public Health professionals working with deprived neighbourhoods would be better to focus on what neighbourhoods have or could develop as social capital for living well, rather than on the vague and tangential notion of community resilience.</p

Effects of adding natural sounds to urban noises on the perceived loudness of noise and soundscape quality

Introducing pleasant natural sounds to mask urban noises is an important soundscape design strategy to improve acoustic comfort. This study investigates the effects of signal-to-noise ratio (SNR) between natural sounds (signal) and the target noises (noise) and their temporal characteristics on the perceived loudness of noise (PLN) and overall soundscape quality (OSQ) through a laboratory experiment. Two types of urban noise sources (hydraulic breaker and traffic noises) were set to A-weighted equivalent sound pressure levels (SPL) of 55, 65, and 75 dB and then augmented with two types of natural sounds (birdsong and stream), across a range of SNRs. Each acoustic stimulus was a combination of noise and natural sound at SNRs from −6 to 6 dB. Averaged across all cases, the subjective assessment of PLN showed that augmenting urban noise separately with the two natural sounds reduced the PLN by 17.9%, with no significant differences found between the birdsong and stream sounds. Adding natural sounds increased the OSQ by on average 18.3% across the cases, but their effects gradually decreased as the noise level increased. The OSQ of the birdsong and stream sounds were similar for traffic noise, whereas the stream sound was rated higher than the birdsong for the breaker noise. The results suggest that increasing the dissimilarity in temporal structure between the target noise and natural sounds could enhance the soundscape quality. Appropriate SNRs were explored considering both PLN and OSQ. The results showed that the SNR of −6 dB was desirable when the A-weighted SPL of the noise rose to 75 dB

Serum Metabolome and Lipidome Changes in Adult Patients with Primary Dengue Infection

10.1371/journal.pntd.0002373PLoS Neglected Tropical Diseases78

A mixed-reality approach to soundscape assessment of outdoor urban environments augmented with natural sounds

To investigate the effect of augmenting natural sounds in noisy environments, an in-situ experiment was conducted using a mixed-reality head-mounted display (MR HMD). Two outdoor locations close to an expressway were selected for the experiment. A natural sound (birdsong or stream) along with a hologram (sparrow/fountain or loudspeaker) was projected through the MR HMD. Participants were asked to adjust the natural sound levels to their preferred level under ambient traffic noise conditions at each location. Participants also assessed the perceived loudness of traffic (PLN) and overall soundscape quality (OSQ) in conditions with and without the augmented natural sounds. The results showed that both natural sounds significantly reduced the PLN and enhanced the OSQ. No significant differences in subjective responses were found between the loudspeaker and visual representations of the natural sound source as holograms. Analysis on the preferred signal-to-noise ratio (SNR), i.e. ratio of natural sound to traffic levels, indicated a strong negative correlation between the preferred SNRs and ambient traffic noise levels. Overall, the preferred SNR of the birdsong was significantly higher than that of the water sound. Among the acoustic parameters tested, the A-weighted traffic noise level was the strongest predictor for the preferred SNR of both the birdsong and water sound. However, the correlation for the water sound was relatively higher than the birdsong. This was due to the larger variance in the subjective evaluation for the birdsong

Effects of contexts in urban residential areas on the pleasantness and appropriateness of natural sounds

Before introducing natural sounds to potentially improve the soundscape quality, it is important to understand how key contextual factors (i.e. expected activities and audio-visual congruency) affect the soundscape in a given location. In this study, the perception of eight natural sounds (i.e. 4 birdsongs, 4 water sounds) at five urban recreational areas under the constant influence of road traffic was explored subjectively under three laboratory settings: visual-only, audio-only, and audio-visual. Firstly, expected socio-recreational activities of each location were determined in the visual-only setting. Subsequently, participants assessed the pleasantness and appropriateness of the soundscape at each site, for each of the eight natural sounds augmented to the same road traffic noise, in both audio-only and audio-visual settings. Interestingly, it was found that the expected activities in each location did not significantly affect natural sound perception, whereas audio-visual congruency of the locations significantly affected the pleasantness and appropriateness of the natural sounds. Particularly, the pleasantness and appropriateness decreased for water sounds when water features were not visually present. In contrast, perception with birdsongs was unaffected by their visibility likely due to the presence of vegetation. Hence, audio-visual coherence is central to the perception of natural sounds in outdoor spaces