There are numerous reference equations available for the single-breath transfer factor of the lung for carbon monoxide (
); however, it is not always clear which reference set should be used in ...clinical practice. The aim of the study was to develop the Global Lung Function Initiative (GLI) all-age reference values for
Data from 19 centres in 14 countries were collected to define
reference values. Similar to the GLI spirometry project, reference values were derived using the LMS (lambda, mu, sigma) method and the GAMLSS (generalised additive models for location, scale and shape) programme in R.12 660
measurements from asymptomatic, lifetime nonsmokers were submitted; 85% of the submitted data were from Caucasians. All data were uncorrected for haemoglobin concentration. Following adjustments for elevation above sea level, gas concentration and assumptions used for calculating the anatomic dead space volume, there was a high degree of overlap between the datasets. Reference values for Caucasians aged 5-85 years were derived for
, transfer coefficient of the lung for carbon monoxide and alveolar volume.This is the largest collection of normative
data, and the first global reference values available for
.
Spirometry is the most common pulmonary function test. It is widely used in the assessment of lung function to provide objective information used in the diagnosis of lung diseases and monitoring lung ...health. In 2005, the American Thoracic Society and the European Respiratory Society jointly adopted technical standards for conducting spirometry. Improvements in instrumentation and computational capabilities, together with new research studies and enhanced quality assurance approaches, have led to the need to update the 2005 technical standards for spirometry to take full advantage of current technical capabilities.
This spirometry technical standards document was developed by an international joint task force, appointed by the American Thoracic Society and the European Respiratory Society, with expertise in conducting and analyzing pulmonary function tests, laboratory quality assurance, and developing international standards. A comprehensive review of published evidence was performed. A patient survey was developed to capture patients' experiences.
Revisions to the 2005 technical standards for spirometry were made, including the addition of factors that were not previously considered. Evidence to support the revisions was cited when applicable. The experience and expertise of task force members were used to develop recommended best practices.
Standards and consensus recommendations are presented for manufacturers, clinicians, operators, and researchers with the aims of increasing the accuracy, precision, and quality of spirometric measurements and improving the patient experience. A comprehensive guide to aid in the implementation of these standards was developed as an online supplement.
This document provides an update to the European Respiratory Society (ERS)/American Thoracic Society (ATS) technical standards for single-breath carbon monoxide uptake in the lung that was last ...updated in 2005. Although both D
(diffusing capacity) and T
(transfer factor) are valid terms to describe the uptake of carbon monoxide in the lung, the term D
is used in this document. A joint taskforce appointed by the ERS and ATS reviewed the recent literature on the measurement of D
and surveyed the current technical capabilities of instrumentation being manufactured around the world. The recommendations in this document represent the consensus of the taskforce members in regard to the evidence available for various aspects of D
measurement. Furthermore, it reflects the expert opinion of the taskforce members on areas in which peer-reviewed evidence was either not available or was incomplete. The major changes in these technical standards relate to D
measurement with systems using rapidly responding gas analysers for carbon monoxide and the tracer gas, which are now the most common type of D
instrumentation being manufactured. Technical improvements and the increased capability afforded by these new systems permit enhanced measurement of D
and the opportunity to include other optional measures of lung function.
SCOPE: Grape seed polyphenol extract (GSPE) is receiving increasing attention for its potential preventative and therapeutic roles in Alzheimer's disease (AD) and other age‐related neurodegenerative ...disorders. The intestinal microbiota is known to actively convert many dietary polyphenols, including GSPE, to phenolic acids. There is limited information on the bioavailability and bioactivity of GSPE‐derived phenolic acid in the brain. METHODS AND RESULTS: We orally administered GSPE to rats and investigated the bioavailability of 12 phenolic acids known to be generated by microbiota metabolism of anthocyanidins. GSPE treatment significantly increased the content of two of the phenolic acids in the brain: 3‐hydroxybenzoic acid and 3‐(3´‐hydroxyphenyl)propionic acid, resulting in the brain accumulations of the two phenolic acids at micromolar concentrations. We also provided evidence that 3‐hydroxybenzoic acid and 3‐(3´‐hydroxyphenyl)propionic acid potently interfere with the assembly of β‐amyloid peptides into neurotoxic β‐amyloid aggregates that play key roles in AD pathogenesis. CONCLUSION: Our observation suggests important contribution of the intestinal microbiota to the protective activities of GSPE (as well as other polyphenol preparations) in AD. Outcomes from our studies support future preclinical and clinical investigations exploring the potential contributions of the intestinal microbiota in protecting against the onset/progression of AD and other neurodegenerative conditions.
Precise genome-editing relies on the repair of sequence-specific nuclease-induced DNA nicking or double-strand breaks (DSBs) by homology-directed repair (HDR). However, nonhomologous end-joining ...(NHEJ), an error-prone repair, acts concurrently, reducing the rate of high-fidelity edits. The identification of genome-editing conditions that favor HDR over NHEJ has been hindered by the lack of a simple method to measure HDR and NHEJ directly and simultaneously at endogenous loci. To overcome this challenge, we developed a novel, rapid, digital PCR-based assay that can simultaneously detect one HDR or NHEJ event out of 1,000 copies of the genome. Using this assay, we systematically monitored genome-editing outcomes of CRISPR-associated protein 9 (Cas9), Cas9 nickases, catalytically dead Cas9 fused to FokI, and transcription activator-like effector nuclease at three disease-associated endogenous gene loci in HEK293T cells, HeLa cells, and human induced pluripotent stem cells. Although it is widely thought that NHEJ generally occurs more often than HDR, we found that more HDR than NHEJ was induced under multiple conditions. Surprisingly, the HDR/NHEJ ratios were highly dependent on gene locus, nuclease platform, and cell type. The new assay system, and our findings based on it, will enable mechanistic studies of genome-editing and help improve genome-editing technology.
Scope Grape seed polyphenol extract (GSPE) is receiving increasing attention for its potential preventative and therapeutic roles in Alzheimer's disease (AD) and other age-related neurodegenerative ...disorders. The intestinal microbiota is known to actively convert many dietary polyphenols, including GSPE, to phenolic acids. There is limited information on the bioavailability and bioactivity of GSPE-derived phenolic acid in the brain. Methods and results We orally administered GSPE to rats and investigated the bioavailability of 12 phenolic acids known to be generated by microbiota metabolism of anthocyanidins. GSPE treatment significantly increased the content of two of the phenolic acids in the brain: 3-hydroxybenzoic acid and 3-(3-hydroxyphenyl)propionic acid, resulting in the brain accumulations of the two phenolic acids at micromolar concentrations. We also provided evidence that 3-hydroxybenzoic acid and 3-(3-hydroxyphenyl)propionic acid potently interfere with the assembly of beta-amyloid peptides into neurotoxic beta-amyloid aggregates that play key roles in AD pathogenesis. Conclusion Our observation suggests important contribution of the intestinal microbiota to the protective activities of GSPE (as well as other polyphenol preparations) in AD. Outcomes from our studies support future preclinical and clinical investigations exploring the potential contributions of the intestinal microbiota in protecting against the onset/progression of AD and other neurodegenerative conditions.
Phenylalanine is a vital component of proteins in all living organisms, and in plants is a precursor for thousands of additional metabolites. Animals are incapable of synthesizing phenylalanine and ...must primarily obtain it directly or indirectly from plants. Although plants can synthesize phenylalanine in plastids through arogenate, the contribution of an alternative pathway via phenylpyruvate, as occurs in most microbes, has not been demonstrated. Here we show that plants also utilize a microbial-like phenylpyruvate pathway to produce phenylalanine, and flux through this route is increased when the entry point to the arogenate pathway is limiting. Unexpectedly, we find the plant phenylpyruvate pathway utilizes a cytosolic aminotransferase that links the coordinated catabolism of tyrosine to serve as the amino donor, thus interconnecting the extra-plastidial metabolism of these amino acids. This discovery uncovers another level of complexity in the plant aromatic amino acid regulatory network, unveiling new targets for metabolic engineering.
Neisseria gonorrhoeae is a high-priority pathogen of concern due to the growing prevalence of resistance development against approved antibiotics. Herein, we report the anti-gonococcal activity of ...ethoxzolamide, the FDA-approved human carbonic anhydrase inhibitor. Ethoxzolamide displayed an MIC
50,
against a panel of N. gonorrhoeae isolates, of 0.125 µg/mL, 16-fold more potent than acetazolamide, although both molecules exhibited almost similar potency against the gonococcal carbonic anhydrase enzyme (NgCA) in vitro. Acetazolamide displayed an inhibition constant (K
i
) versus NgCA of 74 nM, while Ethoxzolamide
'
s K
i
was estimated to 94 nM. Therefore, the increased anti-gonococcal potency of ethoxzolamide was attributed to its increased permeability in N. gonorrhoeae as compared to that of acetazolamide. Both drugs demonstrated bacteriostatic activity against N. gonorrhoeae, exhibited post-antibiotic effects up to 10 hours, and resistance was not observed against both. Taken together, these results indicate that acetazolamide and ethoxzolamide warrant further investigation for translation into effective anti-N. gonorrhoeae agents.
Proteome and metabolome changes in muscles from callipyge mutation (+/C) and non-callipyge phenotype (+/+, C/+, and C/C) lambs were profiled to provide insight into the biochemical changes affecting ...meat quality attributes. M. longissimus thoracis from lambs with all four possible callipyge genotype (n = 4, C/+, C/C, +/C, and +/+) were collected after 3d aging and analyzed using mass-spectrometry based platforms. Among identified proteomes, cytochrome c (pro-apoptotic protein) was detected with significantly lower abundances in +/C. Anti-apoptotic HSP70, BAG3, and PARK7 were over-abundant in +/C, which could result in delayed apoptosis and possibly attributed to tougher meat in callipyge lambs. Eight glycolysis enzymes were overabundant in +/C lambs, whereas 3 enzymes involved in TCA cycle were overabundant in non-callipyge ones (C/C and/or C/+). Twenty-five metabolites were affected by genotypes (P < .05), including metabolic co-factors, polyphenols, and AA/short peptides. Our omics results provided insightful information for revealing the differences in biochemical attributes caused by callipyge mutation.
•Omics was used to reveal molecular changes in muscles form four callipyge genotypes.•Callipyge loins showed distinct proteome profiles compared to the other genotypes.•Twenty-five metabolites were significantly affected by different genotypes.•Synergistic alternations of energy metabolism and key proteins were identified.
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•Greater abundance of flavor-precursors was found in dry-aged beef.•More glutamate containing dipeptides and nucleotides were found in dry-aged beef.•Increases in volatile compounds ...in dry-aged beef were identified.•Dry-aging lowered metabolites related to undesirable flavor such as terpenoids.•Glutathione metabolism could be attributed to dry-aged flavor generation.
The present study was conducted to identify flavor-related chemical compounds and to elucidate beef flavor development in response to dry-aging. Paired grass-fed beef loins (n = 18) were obtained at 7 d postmortem, cut into two sections and assigned to 3 aging methods: conventional dry-aging (DA), vacuum packaged wet-aging (WA) and dry-aging in a bag (DW) for 28 days. Following aging, samples were analyzed for UPLC-MS metabolomics, volatile, fatty acid profiling, and consumer sensory comment analysis. Greater number of proteins and nucleotides derived metabolites were liberated in dry-aged samples compared to WA (P < 0.05). In particular, the liberation of gammaglutmayl peptides and glutamine metabolites through the glutathione metabolism were identified. While fatty acid profile was not affected by treatments (P > 0.05), higher concentrations of volatile compounds were found in the dry-aged (P < 0.05). Dry-aging process decreased the presence of terpenoid and steroid lipid group, which could possibly result in reducing undesirable flavor of grass-fed beef.
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