1,503 research outputs found
Use of 2-dimensional speckle-tracking echocardiography to assess left ventricular systolic function in dogs with systemic inflammatory response syndrome
Background: Early identification of systolic dysfunction in dogs with systemic inflammatory response syndrome (SIRS) potentially could improve the outcome and decrease mortality.
Objective: To compare 2-dimensional speckle tracking (2D-STE) with 2-dimensional (2D) and M-mode echocardiography in the evaluation of systolic function in SIRS dogs.
Animals: Seventeen SIRS and 17 healthy dogs.
Methods: Prospective observational case-control study. Each dog underwent physical examination, conventional echocardiography, 2D-STE, and C-reactive protein measurement.
Results: Dogs with SIRS had lower 2D-STE ejection fraction (X4D-EF; 44 ± 8 versus 53 ± 8; P =.003), endocardial global longitudinal strain (ENDO-G-Long-St; -14.6 ± 3.2 versus -18.5 ± 4.1; P =.003), and normalized left ventricular diameter in diastole (1.38 ± 0.25 versus 1.54 ± 0.17; P =.04) and systole (0.85 ± 0.18 versus 0.97 ± 0.11; P =.03) as compared to healthy dogs. Simpson method of disks (SMOD) right parasternal EF (55 ± 9 versus 60 ± 6; P =.07) and end systolic volume index (ESVI; 23 ± 10 versus 21 ± 6; P =.61), SMOD left apical EF (59 ± 9 versus 59 ± 6; P =.87) and ESVI (20 ± 8 versus 22 ± 6; P =.25), fractional shortening (FS; 34 ± 5 versus 33 ± 4; P =.39), M-mode EF (64 ± 7 versus 62 ± 5; P =.35), and ESVI (23 ± 11 versus 30 ± 9; P =.06) were not significantly different between SIRS and control group, respectively.
Conclusion and Clinical Importance: Speckle tracking X4D-EF and ENDO-G-Long-St are more sensitive than 2D and M-Mode FS, EF, and ESVI in detecting systolic impairment in dogs with SIRS
The Origin of Amerindians and the Peopling of the Americas According to HLA Genes: Admixture with Asian and Pacific People
The classical three-waves theory of American peopling through Beringia was based on a mixed anthropological and linguistic methodology. The use of mtDNA, Y chromosome and other DNA markers offers different results according to the different markers and methodologies chosen by different authors. At present, the peopling of Americas remains uncertain, regarding: time of population, number of peopling waves and place of peopling entrance among other related issues. In the present review, we have gathered most available HLA data already obtained about First Native American populations, which raise some doubts about the classical three waves of American peopling hypothesis. In summary, our conclusions are: 1) North West Canadian Athabaskans have had gene flow with: a) close neighboring populations, b) Amerindians, c) Pacific Islanders including East Australians and d) Siberians; 2) Beringia was probably not the only entrance of people to America: Pacific Ocean boat trips may have contributed to the HLA genetic American profile (or the opposite could also be true); 3) Amerindians entrance to America may have been different to that of Athabaskans and Eskimos and Amerindians may have been in their lands long before Athabaskans and Eskimos because they present and altogether different set of HLA-DRB1 allele frequencies; 4) Amerindians show very few “particular alleles”, almost all are shared with other Amerindians, Athabaskans and Pacific Islanders, including East Australians and Siberians; 5) Our results do not support the three waves model of American peopling, but another model where the people entrance is not only Beringia, but also Pacific Coast. Reverse migration (America to Asia) is not discarded and different movements of people in either direction in different times are supported by the Athabaskan population admixture with Asian-Pacific population and with Amerindians, 6) HLA variability is more common than allele veriability in Amerindians. Finally, it is shown that gene genealogy analises should be completed with allele frequency analyses in population relatednes and migrations studies
Immune-system-dependent anti-tumor activity of a plant-derived polyphenol rich fraction in a melanoma mouse model.
Recent findings suggest that part of the anti-tumor effects of several chemotherapeutic agents require an intact immune system. This is in part due to the induction of immunogenic cell death. We have identified a gallotannin-rich fraction, obtained from Caesalpinia spinosa (P2Et) as an anti-tumor agent in both breast carcinoma and melanoma. Here, we report that P2Et treatment results in activation of caspase 3 and 9, mobilization of cytochrome c and externalization of annexin V in tumor cells, thus suggesting the induction of apoptosis. This was preceded by the onset of autophagy and the expression of immunogenic cell death markers. We further demonstrate that P2Et-treated tumor cells are highly immunogenic in vaccinated mice and induce immune system activation, clearly shown by the generation of interferon gamma (IFN-γ) producing tyrosine-related protein 2 antigen-specific CD8+ T cells. Moreover, the tumor protective effects of P2Et treatment were abolished in immunodeficient mice, and partially lost after CD4 and CD8 depletion, indicating that P2Et's anti-tumor activity is highly dependent on immune system and at least in part of T cells. Altogether, these results support the hypothesis that the gallotannin-rich fraction P2Et's anti-tumor effects are mediated to a great extent by the endogenous immune response following to the exposure to immunogenic dying tumor cells
Epigenetic Signatures Associated with Different Levels of Differentiation Potential in Human Stem Cells
The therapeutic use of multipotent stem cells depends on their differentiation potential, which has been
shown to be variable for different populations. These differences are likely to be the result of key changes in their epigenetic
profiles
Selenium and impaired physical function in US and Spanish older adults
Background: Selenium (Se) is a trace element with a narrow safety margin.
Objectives: To evaluate the cross-sectional and longitudinal dose-response association between Se exposure and
measures of impaired physical function and disability in older adults.
Design: NHANES 2011–2014 cross-sectional (US, n = 1733, age ≥60 years) and Seniors-ENRICA-2 2017–2019
cross-sectional and longitudinal (Spain, n = 2548 and 1741, respectively, age ≥65 years) data were analyzed.
Whole blood and serum Se levels were measured using inductively coupled plasma-mass spectrometry. Lowerextremity
performance was assessed with the Short Physical Performance Battery, and muscle weakness with
a dynamometer. Incident mobility and agility limitations, and disability in instrumental activities of daily living
(IADL) were ascertained with standardized questionnaires. Analyses were adjusted for relevant confounders,
including physical activity. Results across studies were pooled using random-effects meta-analysis.
Results: Meta-analyzed odds ratios (95% confidence interval) per log2 increase in whole blood Se were 0.54
(0.32; 0.76) for weakness, 0.59 (0.34; 0.83) for impaired lower-extremity performance, 0.48 (0.31; 0.68) for
mobility limitations, 0.71 (0.45; 0.97) for agility limitations, and 0.34 (0.12; 0.56) for disability in at least one
IADL. Analyses for serum Se in NHANES showed similar results. Findings suggest the inverse association with
grip strength is progressive below 140 μg/L (p-value for non-linear trend in the Seniors-ENRICA-2 study = 0.13),
and above 140 μg/L (p-value for non-linear trend in NHANES = 0.11). In the Seniors-ENRICA-2 cohort, with a
2.2 year follow-up period, a doubling in baseline Se levels were associated with a lower incidence of weakness
[odds ratio (95% confidence interval): 0.45 (0.22; 0.91)], impaired lower-extremity performance [0.63 (0.32;
1.23)], mobility [0.43 (0.21; 0.91)] and agility [0.38 (0.18; 0.78)] limitations.
Discussion: In US and Spanish older adults, Se concentrations were inversely associated with physical function
limitations. Further studies are needed to elucidate underlying mechanisms.Instituto de Salud Carlos III
European Commission
PI18/287
16/609State Secretary of R + D + I
PID2019-108973RB-C21/C22European Social Fund (ESF)
European Commissio
Generation and efficacy assessment of a chimeric antigen E2-CD154 as a marker Classical Swine Fever Virus subunit vaccine produced in HEK 293 and CHO K1 mammalian cells
The E2 glycoprotein is the major antigen that induces neutralizing and protective antibodies in CSFV infected pigs, thus a marker vaccine based on this antigen appears to be the most promising alternative to induce a protective immune response against CSFV. However, the structural characteristics of this protein state the necessity to produce glycoprotein E2 in more complex expression systems such as mammalian cells. In this study, we use a lentivirus-based gene delivery system to establish a stable recombinant HEK 293 and CHO K1 cell line for the expression of E2 fused to porcine CD154 as immunostimulatory molecule. In a first experiment, E2his and E2-CD154 were compared in an immunization trial. The average antibody titers in E2his immunized pigs was in the range of 30-40% of blocking and the average antibody titers for E2-CD154 are above 40% at day 14, meaning that the chimeric antigen is able to raise antibodies at positive levels in a shorter time. Additionally, the blocking rate of E2his vaccinated group in ELISA ranged between 66-88% and in the E2-CD154- vaccinated groups ranged between 86-92%, one week after booster immunization. The NPLA antibody titers also increased greatly. Later on, the protective capacity of purified E2-CD154 glycoprotein was demonstrated in a challenge experiment in pigs using a biphasic immunization schedule with 25 and 50 μg. The immunized animals developed neutralizing antibodies that were protective when the animals were faced to a challenge with 105 LD50 of ‘‘Margarita’’ CSFV highly pathogenic strain. No clinical signs of the disease were detected in the vaccinated pigs. Unvaccinated pigs in the control group exhibited symptoms of CSF at 3–4 days after challenge and were euthanized from 7–9 days when the pigs became moribund. These results indicate that E2-CD154 produced in recombinant HEK 293 and CHOK1cell line is a high quality candidate for the development of a safe and effective CSFV subunit vaccine. In the next steps, pilot and production scale, E2-CD154 expression levels should be increased in 10 to 50 fold, arriving to a very attractive productive platform for an implementation of a commercial subunit vaccine against CSF
Observed Consequences of Presupernova Instability in Very Massive Stars
This chapter concentrates on the deaths of very massive stars, the events
leading up to their deaths, and how mass loss affects the resulting death. The
previous three chapters emphasized the theory of wind mass loss, eruptions, and
core collapse physics, but here we emphasize mainly the observational
properties of the resulting death throes. Mass loss through winds, eruptions,
and interacting binaries largely determines the wide variety of different types
of supernovae that are observed, as well as the circumstellar environments into
which the supernova blast waves expand. Connecting these observed properties of
the explosions to the initial masses of their progenitor stars is, however, an
enduring challenge and is especially difficult for very massive stars.
Superluminous supernovae, pair instability supernovae, gamma ray bursts, and
"failed" supernovae are all end fates that have been proposed for very massive
stars, but the range of initial masses or other conditions leading to each of
these (if they actually occur) are still very certain. Extrapolating to infer
the role of very massive stars in the early universe is essentially
unencumbered by observational constraints and still quite dicey.Comment: 39 pages, 5 figures, to appear as chapter in the book "Very Massive
Stars in the Local Universe", ed. J. Vin
Endothelial Progenitor Cells as a Potential Biomarker in Interstitial Lung Disease Associated with Rheumatoid Arthritis
Interstitial lung disease (ILD) increases morbidity and mortality in patients with rheumatoid arthritis (RA). Although the pathogenesis of ILD associated with RA (RA-ILD(+)) remains poorly defined, vascular tissue is crucial in lung physiology. In this context, endothelial progenitor cells (EPC) are involved in endothelial tissue repair. However, little is known about their implication in RA-ILD(+). Accordingly, we aimed to investigate the potential role of EPC related to endothelial damage in RA-ILD(+). EPC quantification in peripheral blood from 80 individuals (20 RA-ILD(+) patients, 25 RA-ILD(-) patients, 21 idiopathic pulmonary fibrosis (IPF) patients, and 14 healthy controls) was performed by flow cytometry. EPC were considered as CD34(+), CD45(low), CD309(+) and CD133(+). A significant increase in EPC frequency in RA-ILD(+) patients, as well as in RA-ILD(-) and IPF patients, was found when compared with controls (p < 0.001, p = 0.02 and p < 0.001, respectively). RA-ILD(+) patients exhibited a higher EPC frequency than the RA-ILD(-) ones (p = 0.003), but lower than IPF patients (p < 0.001). Our results suggest that EPC increase may represent a reparative compensatory mechanism in patients with RA-ILD(+). The degree of EPC frequency may help to identify the presence of ILD in RA patients and to discriminate RA-ILD(+) from IPF
HLA association with the susceptibility to anti-synthetase syndrome
Objective: To investigate the human leukocyte antigen (HLA) association with anti-synthetase syndrome (ASSD). Methods: We conducted the largest immunogenetic HLA-DRB1 and HLA-B study to date in a homogeneous cohort of 168 Caucasian patients with ASSD and 486 ethnically matched healthy controls by sequencing-based-typing. Results: A statistically significant increase of HLA-DRB1*03:01 and HLA-B*08:01 alleles in patients with ASSD compared to healthy controls was disclosed (26.2% versus 12.2%, P = 1.56E–09, odds ratio–OR [95% confidence interval–CI] = 2.54 [1.84–3.50] and 21.4% versus 5.5%, P = 18.95E–18, OR [95% CI] = 4.73 [3.18–7.05]; respectively). Additionally, HLA-DRB1*07:01 allele was significantly decreased in patients with ASSD compared to controls (9.2% versus 17.5%, P = 0.0003, OR [95% CI] = 0.48 [0.31–0.72]). Moreover, a statistically significant increase of HLA-DRB1*03:01 allele in anti-Jo-1 positive compared to anti-Jo-1 negative patients with ASSD was observed (31.8% versus 15.5%, P = 0.001, OR [95% CI] = 2.54 [1.39–4.81]). Similar findings were observed when HLA carrier frequencies were assessed. The HLA-DRB1*03:01 association with anti-Jo-1 was unrelated to smoking history. No HLA differences in patients with ASSD stratified according to the presence/absence of the most representative non-anti-Jo-1 anti-synthetase autoantibodies (anti-PL-12 and anti-PL-7), arthritis, myositis or interstitial lung disease were observed. Conclusions: Our results support the association of the HLA complex with the susceptibility to ASSD
WEBT and XMM-Newton observations of 3C 454.3 during the post-outburst phase. Detection of the little and big blue bumps
The blazar 3C 454.3 underwent an unprecedented optical outburst in spring
2005. This was first followed by a mm and then by a cm radio outburst, which
peaked in February 2006. We report on follow-up observations by the WEBT to
study the multiwavelength emission in the post-outburst phase. XMM-Newton
observations on July and December 2006 added information on the X-ray and UV
fluxes. The source was in a faint state. The radio flux at the higher
frequencies showed a fast decreasing trend, which represents the tail of the
big radio outburst. It was followed by a quiescent state, common at all radio
frequencies. In contrast, moderate activity characterized the NIR and optical
light curves, with a progressive increase of the variability amplitude with
increasing wavelength. We ascribe this redder-when-brighter behaviour to the
presence of a "little blue bump" due to line emission from the broad line
region, which is clearly visible in the source SED during faint states.
Moreover, the data from the XMM-Newton OM reveal a rise of the SED in the UV,
suggesting the existence of a "big blue bump" due to thermal emission from the
accretion disc. The X-ray spectra are well fitted with a power-law model with
photoelectric absorption, possibly larger than the Galactic one. However, the
comparison with previous X-ray observations would imply that the amount of
absorbing matter is variable. Alternatively, the intrinsic X-ray spectrum
presents a curvature, which may depend on the X-ray brightness. In this case,
two scenarios are possible.Comment: 9 pages, 7 figures, accepted for publication in A&
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