Although substantial evidence has established that microglia and astrocytes play a key role in the establishment and maintenance of persistent pain in animal models, the role of glial cells in human ...pain disorders remains unknown. Here, using the novel technology of integrated positron emission tomography-magnetic resonance imaging and the recently developed radioligand (11)C-PBR28, we show increased brain levels of the translocator protein (TSPO), a marker of glial activation, in patients with chronic low back pain. As the Ala147Thr polymorphism in the TSPO gene affects binding affinity for (11)C-PBR28, nine patient-control pairs were identified from a larger sample of subjects screened and genotyped, and compared in a matched-pairs design, in which each patient was matched to a TSPO polymorphism-, age- and sex-matched control subject (seven Ala/Ala and two Ala/Thr, five males and four females in each group; median age difference: 1 year; age range: 29-63 for patients and 28-65 for controls). Standardized uptake values normalized to whole brain were significantly higher in patients than controls in multiple brain regions, including thalamus and the putative somatosensory representations of the lumbar spine and leg. The thalamic levels of TSPO were negatively correlated with clinical pain and circulating levels of the proinflammatory citokine interleukin-6, suggesting that TSPO expression exerts pain-protective/anti-inflammatory effects in humans, as predicted by animal studies. Given the putative role of activated glia in the establishment and or maintenance of persistent pain, the present findings offer clinical implications that may serve to guide future studies of the pathophysiology and management of a variety of persistent pain conditions.
We investigate the inner regions of the Milky Way using data from APOGEE and
Gaia
EDR3. Our inner Galactic sample has more than 26 500 stars within |
X
Gal
|< 5 kpc, |
Y
Gal
|< 3.5 kpc, |
Z
Gal
|< 1 ...kpc, and we also carry out the analysis for a foreground-cleaned subsample of 8000 stars that is more representative of the bulge–bar populations. These samples allow us to build chemo-dynamical maps of the stellar populations with vastly improved detail. The inner Galaxy shows an apparent chemical bimodality in key abundance ratios
α
/Fe, C/N, and Mn/O, which probe different enrichment timescales, suggesting a star formation gap (quenching) between the high- and low-
α
populations. Using a joint analysis of the distributions of kinematics, metallicities, mean orbital radius, and chemical abundances, we can characterize the different populations coexisting in the innermost regions of the Galaxy for the first time. The chemo-kinematic data dissected on an eccentricity–|
Z
|
max
plane reveal the chemical and kinematic signatures of the bar, the thin inner disc, and an inner thick disc, and a broad metallicity population with large velocity dispersion indicative of a pressure-supported component. The interplay between these different populations is mapped onto the different metallicity distributions seen in the eccentricity–|
Z
|
max
diagram consistently with the mean orbital radius and
V
ϕ
distributions. A clear metallicity gradient as a function of |
Z
|
max
is also found, which is consistent with the spatial overlapping of different populations. Additionally, we find and chemically and kinematically characterize a group of counter-rotating stars that could be the result of a gas-rich merger event or just the result of clumpy star formation during the earliest phases of the early disc that migrated into the bulge. Finally, based on 6D information, we assign stars a probability value of being on a bar orbit and find that most of the stars with large bar orbit probabilities come from the innermost 3 kpc, with a broad dispersion of metallicity. Even stars with a high probability of belonging to the bar show chemical bimodality in the
α
/Fe versus Fe/H diagram. This suggests bar trapping to be an efficient mechanism, explaining why stars on bar orbits do not show a significant, distinct chemical abundance ratio signature.
Drosophila suzukii (Matsumura) is a species native to Western Asia that is able to pierce intact fruit during egg laying, causing it to be considered a fruit crop pest in many countries. Drosophila ...suzukii have a rapid expansion worldwide; occurrences were recorded in North America and Europe in 2008, and South America in 2013. Due to this rapid expansion, we modeled the potential distribution of this species using the Maximum Entropy Modeling (MaxEnt) algorithm and the Genetic Algorithm for Ruleset Production (GARP) using 407 sites with known occurrences worldwide and 11 predictor variables. After 1000 replicates, the value of the average area under the curve (AUC) of the model predictions with 1000 replicates was 0.97 for MaxEnt and 0.87 for GARP, indicating that both models had optimal performances. The environmental variables that most influenced the prediction of the MaxEnt model were the annual mean temperature, the maximum temperature of the warmest month, the mean temperature of the coldest quarter and the annual precipitation. The models indicated high environmental suitability, mainly in temperate and subtropical areas in the continents of Asia, Europe and North and South America, where the species has already been recorded. The potential for further invasions of the African and Australian continents is predicted due to the environmental suitability of these areas for this species.
•Microstructure arrays affect mechanical responses of SnBi, SnAg and SnZn alloys.•Mechanical behavior of solder alloys is compared with that of the Sn–40Pb alloy.•Analysis cost/ weight indexes and ...mechanical properties is proposed to select Pb-free alloys.
The aim of this paper is to develop a comparative evaluation of mechanical properties of as-cast Sn–Bi, Sn–Ag and Sn–Zn alloys as a function of the resulting microstructural arrays with a view to application as solder materials. The resulting microstructures, ultimate and yield tensile strengths and elongations of Sn–40wt.% Bi, Sn–3.5wt.% Ag and Sn–9wt.% Zn alloys were examined and compared with the corresponding results of the traditional Sn–40wt.% Pb solder alloy. Tensile tests were carried out using specimens selected from specific positions along the length of the directionally solidified castings and Hall–Petch type correlations have been proposed relating the resulting tensile properties of each alloy to a parametric scale of the microstructure. It was found that all Pb-free alloys examined comply with a compromise between compatible mechanical strength and environmental protection. The Sn–Bi alloy has the highest ultimate tensile strength of all alloys examined, while both Sn–Ag and Sn–Zn alloys are lighter and exhibited higher ductility than the Sn–Pb and Sn–Bi alloys.
Flow cytometry has become a highly valuable method to monitor minimal residual disease (MRD) and evaluate the depth of complete response (CR) in bone marrow (BM) of multiple myeloma (MM) after ...therapy. However, current flow-MRD has lower sensitivity than molecular methods and lacks standardization. Here we report on a novel next generation flow (NGF) approach for highly sensitive and standardized MRD detection in MM. An optimized 2-tube 8-color antibody panel was constructed in five cycles of design-evaluation-redesign. In addition, a bulk-lysis procedure was established for acquisition of ⩾10
cells/sample, and novel software tools were constructed for automatic plasma cell gating. Multicenter evaluation of 110 follow-up BM from MM patients in very good partial response (VGPR) or CR showed a higher sensitivity for NGF-MRD vs conventional 8-color flow-MRD -MRD-positive rate of 47 vs 34% (P=0.003)-. Thus, 25% of patients classified as MRD-negative by conventional 8-color flow were MRD-positive by NGF, translating into a significantly longer progression-free survival for MRD-negative vs MRD-positive CR patients by NGF (75% progression-free survival not reached vs 7 months; P=0.02). This study establishes EuroFlow-based NGF as a highly sensitive, fully standardized approach for MRD detection in MM which overcomes the major limitations of conventional flow-MRD methods and is ready for implementation in routine diagnostics.
APOGEE-2 is a high-resolution, near-infrared spectroscopic survey observing ∼3 × 105 stars across the entire sky. It is the successor to APOGEE and is part of the Sloan Digital Sky Survey IV ...(SDSS-IV). APOGEE-2 is expanding on APOGEE's goals of addressing critical questions of stellar astrophysics, stellar populations, and Galactic chemodynamical evolution using (1) an enhanced set of target types and (2) a second spectrograph at Las Campanas Observatory in Chile. APOGEE-2 is targeting red giant branch and red clump stars, RR Lyrae, low-mass dwarf stars, young stellar objects, and numerous other Milky Way and Local Group sources across the entire sky from both hemispheres. In this paper, we describe the APOGEE-2 observational design, target selection catalogs and algorithms, and the targeting-related documentation included in the SDSS data releases.
Pseudomonas aeruginosa is one of the most worrisome infectious bacteria due to its intrinsic and acquired resistance against several antibiotics and the recalcitrance of its infections; hence, the ...development of novel antimicrobials effective against multidrug‐resistant P. aeruginosa is mandatory. In this work, silver nanoparticles obtained by green synthesis using a leaf extract and fungi were tested against a battery of clinical strains from cystic fibrosis, pneumonia and burnt patients, some of them with multidrug resistance. Both nanoparticles showed a potent antibacterial effect, causing severe damage to the cell wall, membrane and DNA, and inducing the production of reactive oxygen species. Moreover, the nanoparticles derived from fungi showed synergistic antibacterial effects with the antibiotics meropenem and levofloxacin for some clinical strains and both kinds of nanoparticles were nontoxic for larvae of the moth Galleria mellonella, encouraging further research for their implementation in the treatment of P. aeruginosa infections.
Significance and Impact of the Study: The continuous rise of antibiotic resistance in bacteria such as Pseudomonas aeruginosa is a serious threat to human health, hence it is mandatory to identify novel ways to combat its infections. In this work, silver nanoparticles were synthesized in a green way using leaves and fugal extracts and its antibacterial effects were tested against clinical strains. The nanoparticles killed the strains due severe cellular damage affecting the membranes, the DNA and generating reactive oxygen species, in addition they were nontoxic and displayed synergy with some antibiotics; therefore, being a promising alternative to treat MDR P. aeruginosa infections.
Objectives
To investigate the incidence of clinical, ultrasonographic and biochemical findings related to pre‐eclampsia (PE) in pregnancies with COVID‐19, and to assess their accuracy to ...differentiate between PE and the PE‐like features associated with COVID‐19.
Design
A prospective, observational study.
Setting
Tertiary referral hospital.
Participants
Singleton pregnancies with COVID‐19 at >20+0 weeks.
Methods
Forty‐two consecutive pregnancies were recruited and classified into two groups: severe and non‐severe COVID‐19, according to the occurrence of severe pneumonia. Uterine artery pulsatility index (UtAPI) and angiogenic factors (soluble fms‐like tyrosine kinase‐1/placental growth factor sFlt‐1/PlGF) were assessed in women with suspected PE.
Main outcome measures
Incidence of signs and symptoms related to PE, such as hypertension, proteinuria, thrombocytopenia, elevated liver enzymes, abnormal UtAPI and increased sFlt‐1/PlGF.
Results
Thirty‐four cases were classified as non‐severe and 8 as severe COVID‐19. Five (11.9%) women presented signs and symptoms of PE, all five being among the severe COVID‐19 cases (62.5%). However, abnormal sFlt‐1/PlGF and UtAPI could only be demonstrated in one case. One case remained pregnant after recovery from severe pneumonia and had a spontaneous resolution of the PE‐like syndrome.
Conclusions
Pregnant women with severe COVID‐19 can develop a PE‐like syndrome that might be distinguished from actual PE by sFlt‐1/PlGF, LDH and UtAPI assessment. Healthcare providers should be aware of its existence and monitor pregnancies with suspected pre‐eclampsia with caution.
Tweetable
This study shows that a pre‐eclampsia‐like syndrome could be present in some pregnancies with severe COVID‐19.
Tweetable
This study shows that a pre‐eclampsia‐like syndrome could be present in some pregnancies with severe COVID‐19.
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