The role of airway microbiome in corticosteroid response in asthma is unknown.
To examine airway microbiome composition in patients with corticosteroid-resistant (CR) asthma and compare it with ...patients with corticosteroid-sensitive (CS) asthma and normal control subjects and explore whether bacteria in the airways of subjects with asthma may direct alterations in cellular responses to corticosteroids.
16S rRNA gene sequencing was performed on bronchoalveolar lavage (BAL) samples of 39 subjects with asthma and 12 healthy control subjects. In subjects with asthma, corticosteroid responsiveness was characterized, BAL macrophages were stimulated with pathogenic versus commensal microorganisms, and analyzed by real-time polymerase chain reaction for the expression of corticosteroid-regulated genes and cellular p38 mitogen-activated protein kinase (MAPK) activation.
Of the 39 subjects with asthma, 29 were CR and 10 were CS. BAL microbiome from subjects with CR and CS asthma did not differ in richness, evenness, diversity, and community composition at the phylum level, but did differ at the genus level, with distinct genus expansions in 14 subjects with CR asthma. Preincubation of asthmatic airway macrophages with Haemophilus parainfluenzae, a uniquely expanded potential pathogen found only in CR asthma airways, resulted in p38 MAPK activation, increased IL-8 (P < 0.01), mitogen-activated kinase phosphatase 1 mRNA (P < 0.01) expression, and inhibition of corticosteroid responses (P < 0.05). This was not observed after exposure to commensal bacterium Prevotella melaninogenica. Inhibition of transforming growth factor-β-associated kinase-1 (TAK1), upstream activator of MAPK, but not p38 MAPK restored cellular sensitivity to corticosteroids.
A subset of subjects with CR asthma demonstrates airway expansion of specific gram-negative bacteria, which trigger TAK1/MAPK activation and induce corticosteroid resistance. TAK1 inhibition restored cellular sensitivity to corticosteroids.
High-latitude ecosystems have the capacity to release large amounts of carbon dioxide (CO₂) to the atmosphere in response to increasing temperatures, representing a potentially significant positive ...feedback within the climate system. Here, we combine aircraft and tower observations of atmospheric CO₂ with remote sensing data and meteorological products to derive temporally and spatially resolved year-round CO₂ fluxes across Alaska during 2012–2014. We find that tundra ecosystems were a net source of CO₂ to the atmosphere annually, with especially high rates of respiration during early winter (October through December). Long-term records at Barrow, AK, suggest that CO₂ emission rates from North Slope tundra have increased during the October through December period by 73% ± 11% since 1975, and are correlated with rising summer temperatures. Together, these results imply increasing early winter respiration and net annual emission of CO₂ in Alaska, in response to climate warming. Our results provide evidence that the decadal-scale increase in the amplitude of the CO₂ seasonal cycle may be linked with increasing biogenic emissions in the Arctic, following the growing season. Early winter respiration was not well simulated by the Earth System Models used to forecast future carbon fluxes in recent climate assessments. Therefore, these assessments may underestimate the carbon release from Arctic soils in response to a warming climate.
Background Brain health may be affected by modifiable lifestyle factors; consuming fish and antioxidative omega-3 fatty acids may reduce brain structural abnormality risk. Purpose To determine ...whether dietary fish consumption is related to brain structural integrity among cognitively normal elders. Methods Data were analyzed from 260 cognitively normal individuals from the Cardiovascular Health Study with information on fish consumption from the National Cancer Institute Food Frequency Questionnaire and brain magnetic resonance imaging (MRI). The relationship between fish consumption data collected in 1989–1990 and brain structural MRI obtained in 1998–1999 was assessed using voxel-based morphometry in multiple regression analyses in 2012. Covariates were age, gender, race, education, white matter lesions, MRI-identified infarcts, waist–hip ratio, and physical activity as assessed by the number of city blocks walked in 1 week. Volumetric changes were further modeled with omega-3 fatty acid estimates to better understand the mechanistic link between fish consumption, brain health, and Alzheimer disease. Results Weekly consumption of baked or broiled fish was positively associated with gray matter volumes in the hippocampus, precuneus, posterior cingulate, and orbital frontal cortex even after adjusting for covariates. These results did not change when including omega-3 fatty acid estimates in the analysis. Conclusions Dietary consumption of baked or broiled fish is related to larger gray matter volumes independent of omega-3 fatty acid content. These findings suggest that a confluence of lifestyle factors influence brain health, adding to the growing body of evidence that prevention strategies for late-life brain health need to begin decades earlier.
We present a detailed analysis of techniques to mitigate the effects of phase noise and Doppler-induced frequency offsets in coherent random amplitude modulated continuous-wave (RAMCW) LiDAR. The ...analysis focuses specifically on a technique which uses coherent dual-quadrature detection to enable a sum of squares calculation to remove the input signal's dependence on carrier phase and frequency. This increases the correlation bandwidth of the matched-template filter to the bandwidth of the acquisition system, whilst also supporting the simultaneous measurement of relative radial velocity with unambiguous direction-of-travel. A combination of simulations and experiments demonstrate the sum of squares technique's ability to measure distance with consistently high SNR, more than 15 dB better than alternative techniques whilst operating in the presence of otherwise catastrophic phase noise and large frequency offsets. In principle, the technique is able to mitigate any sources of phase noise and frequency offsets common to the two orthogonal outputs of a coherent dual-quadrature receiver including laser frequency noise, speckle-induced phase noise, and Doppler frequency shifts due to accelerations.
This paper presents an analytical model and experimental validation for the detection performance and false-alarm rates for phase-encoded random modulation continuous-wave (RMCW) LiDAR. Derivation of ...the model focuses on propagating the effects of relevant noise sources through the system to determine an analytical expression for the detection rate, expressed by the probability of detection. The model demonstrates that probability of detection depends only on three factors: i) the mean signal-to-noise ratio (SNR) of the measurement; ii) the measurement integration time; and iii) speckle-induced intensity noise. The predicted analytical relationship between measurement SNR and probability of detection was validated by numerical simulations and experimental demonstrations in both a controlled fiber channel and under fully-developed speckle conditions in an uncontrolled free-space channel.
SeptiCyte
RAPID is a gene expression assay measuring the relative expression levels of host response genes PLA2G7 and PLAC8, indicative of a dysregulated immune response during sepsis. As severe ...forms of COVID-19 may be considered viral sepsis, we evaluated SeptiCyte RAPID in a series of 94 patients admitted to Foch Hospital (Suresnes, France) with proven SARS-CoV-2 infection. EDTA blood was collected in the emergency department (ED) in 67 cases, in the intensive care unit (ICU) in 23 cases and in conventional units in 4 cases. SeptiScore (0-15 scale) increased with COVID-19 severity. Patients in ICU had the highest SeptiScores, producing values comparable to 8 patients with culture-confirmed bacterial sepsis. Receiver operating characteristic (ROC) curve analysis had an area under the curve (AUC) of 0.81 for discriminating patients requiring ICU admission from patients who were immediately discharged or from patients requiring hospitalization in conventional units. SeptiScores increased with the extent of the lung injury. For 68 patients, a chest computed tomography (CT) scan was performed within 24 h of COVID-19 diagnosis. SeptiScore >7 suggested lung injury ≥50% (AUC = 0.86). SeptiCyte RAPID was compared to other biomarkers for discriminating Critical + Severe COVID-19 in ICU, versus Moderate + Mild COVID-19 not in ICU. The mean AUC for SeptiCyte RAPID was superior to that of any individual biomarker or combination thereof. In contrast to C-reactive protein (CRP), correlation of SeptiScore with lung injury was not impacted by treatment with anti-inflammatory agents. SeptiCyte RAPID can be a useful tool to identify patients with severe forms of COVID-19 in ED, as well as during follow-up.
The most commonly used materials used for interbody cages are titanium metal and polymer polyetheretherketone (PEEK). Both of these materials have demonstrated good biocompatibility. A major ...disadvantage associated with solid titanium cages is their radiopacity, limiting the postoperative monitoring of spinal fusion via standard imaging modalities. However, PEEK is radiolucent, allowing for a temporal assessment of the fusion mass by clinicians. On the other hand, PEEK is hydrophobic, which can limit bony ingrowth. Although both PEEK and titanium have demonstrated clinical success in obtaining a solid spinal fusion, innovations are being developed to improve fusion rates and to create stronger constructs using hybrid additive manufacturing approaches by incorporating both materials into a single interbody device.
The purpose of this study was to examine the interbody fusion characteristic of a PEEK Titanium Composite (PTC) cage for use in lumbar fusion.
Thirty-four mature female sheep underwent two-level (L2–L3 and L4–L5) interbody fusion using either a PEEK or a PTC cage (one of each per animal). Animals were sacrificed at 0, 8, 12, and 18 weeks post surgery.
Post sacrifice, each surgically treated functional spinal unit underwent non-destructive kinematic testing, microcomputed tomography scanning, and histomorphometric analyses.
Relative to the standard PEEK cages, the PTC constructs demonstrated significant reductions in ranges of motion and a significant increase in stiffness. These biomechanical findings were reinforced by the presence of significantly more bone at the fusion site as well as ingrowth into the porous end plates.
Overall, the results indicate that PTC interbody devices could potentially lead to a more robust intervertebral fusion relative to a standard PEEK device in a clinical setting.
Silicon photonic biosensors are highly attractive for multiplexed Lab-on-Chip systems. Here, we characterize the sensing performance of 3 µm TE-mode and 10 µm dual TE/TM-mode silicon photonic ...micro-disk resonators and demonstrate their ability to detect the specific capture of biomolecules. Our experimental results show sensitivities of 26 nm/RIU and 142 nm/RIU, and quality factors of 3.3x10(4) and 1.6x10(4) for the TE and TM modes, respectively. Additionally, we show that the large disks contain both TE and TM modes with differing sensing characteristics. Finally, by serializing multiple disks on a single waveguide bus in a CMOS compatible process, we demonstrate a biosensor capable of multiplexed interrogation of biological samples.
Some sources may need to estimate ozone and secondarily formed PM2.5 as part of the permit application process under the Clean Air Act New Source Review program. Photochemical grid models represent ...state-of-the-science gas- and particle-phase chemistry and provide a realistic chemical and physical environment for assessing changes in air quality resulting from changes in emissions. When using these tools for single source impact assessments, it is important to differentiate a single source impact from other emissions sources and to understand how well contemporary grid model applications capture near-source transport and chemistry. Here for the first time, both source apportionment and source sensitivity approaches (brute-force changes and high-order direct decoupled method) are used in a photochemical grid model to isolate impacts of a specific facility. These single source impacts are compared with in-plume measurements made as part of a well-characterized 1999 TVA Cumberland aircraft plume transect field study. The techniques were able to isolate the impacts of the TVA plume in a manner consistent with observations. The model predicted in-plume concentrations well when the observations were averaged to the grid scale, although peak concentrations of primary pollutants were generally underestimated near the source, possibly due to dilution in the 4-km grid cell.
•Photochemical grid model can resolve single source impacts near-source and regionally.•Source sensitivity and apportionment techniques capture single source impacts.•Predict the primary and secondary average source impacts well at 4 km for this case.•Capture downwind ozone production well (mean and peak) at 4 km for this case.•Underpredict near-source ozone titration events and primary pollutant peaks at 4 km.
Tools for the evaluation of COVID-19 severity would help clinicians with triage decisions, especially the decision whether to admit to ICU. The aim of this study was to evaluate SeptiCyte RAPID, a ...host immune response assay (Immunexpress, Seattle USA) as a triaging tool for COVID-19 patients requiring hospitalization and potentially ICU care. SeptiCyte RAPID employs a host gene expression signature consisting of the ratio of expression levels of two immune related mRNAs, PLA2G7 and PLAC8, measured from whole blood samples. Blood samples from 146 adult SARS-CoV-2 (+) patients were collected within 48 h of hospital admission in PAXgene blood RNA tubes at Hospital del Mar, Barcelona, Spain, between July 28th and December 1st, 2020. Data on demographics, vital signs, clinical chemistry parameters, radiology, interventions, and SeptiCyte RAPID were collected and analyzed with bioinformatics methods. The performance of SeptiCyte RAPID for COVID-19 severity assessment and ICU admission was evaluated, relative to the comparator of retrospective clinical assessment by the Hospital del Mar clinical care team. In conclusion, SeptiCyte RAPID was able to stratify COVID-19 cases according to clinical severity: critical vs. mild (AUC = 0.93, p < 0.0001), critical vs. moderate (AUC = 0.77, p = 0.002), severe vs. mild (AUC = 0.85, p = 0.0003), severe vs. moderate (AUC = 0.63, p = 0.05). This discrimination was significantly better (by AUC or p-value) than could be achieved by CRP, lactate, creatine, IL-6, or D-dimer. Some of the critical or severe cases had "early" blood draws (before ICU admission; n = 33). For these cases, when compared to moderate and mild cases not in ICU (n = 37), SeptiCyte RAPID had AUC = 0.78 (p = 0.00012). In conclusion, SeptiCyte RAPID was able to stratify COVID-19 cases according to clinical severity as defined by the WHO COVID-19 Clinical Management Living Guidance of January 25th, 2021. Measurements taken early (before a patient is considered for ICU admission) suggest that high SeptiScores could aid in predicting the need for later ICU admission.
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