We present a detailed X-ray spectral analysis of the sources in the 1Ms catalog of the Chandra Deep Field South (CDFS) taking advantage of optical spectroscopy and photometric redshifts for 321 ...extragalactic sources out of the total sample of 347 sources. As a default spectral model, we adopt a power law with slope Gamma with an intrinsic redshifted absorption N sub(H), a fixed Galactic absorption and an unresolved Fe emission line. For 82 X-ray bright sources, we are able to perform the X-ray spectral analysis leaving both Gamma and N sub(H) free. The weighted mean value for the slope of the power law is < Gamma > 1.75 plus or minus 0.02, and the distribution of best fit values shows an intrinsic dispersion of sigma sub(int) 0.30. We do not find hints of a correlation between the spectral index Gamma and the intrinsic absorption column density N sub(H). We then investigate the absorption distribution for the whole sample, deriving the N sub(H) values in faint sources by fixing Gamma = 1.8. We also allow for the presence of a scattered component at soft energies with the same slope of the main power law, and for a pure reflection spectrum typical of Compton-thick AGN. We detect the presence of a scattered soft component in 8 sources; we also identify 14 sources showing a reflection-dominated spectrum. The latter are referred to as Compton-thick AGN candidates. By correcting for both incompleteness and sampling-volume effects, we recover the intrinsic N sub(H) distribution representative of the whole AGN population, f(N sub(H))dN sub(H), from the observed one. f(N sub(H)) shows a lognormal shape, peaking around log(N sub(H)) 23.1 and wither sigma 1.1. Interestingly, such a distribution shows continuity between the population of Compton-thin and that of Compton-thick AGN. We find that the fraction of absorbed sources (with N sub(H) > 10 super(22) cm super(-2)) in the sample is constant (at the level of about 75%) or moderately increasing with redshift. Finally, we compare the optical classification to the X-ray spectral properties, confirming that the correspondence of unabsorbed (absorbed) X-ray sources to optical type I (type II) AGN is accurate for at least 80% of the sources with spectral identification (1/3 of the total X-ray sample).
The risk for symptomatic COVID-19 requiring hospitalization is higher in the older population. The course of the disease in hospitalised older patients may show significant variation, from mild to ...severe illness, ultimately leading to death in the most critical cases. The analysis of circulating biomolecules involved in mechanisms of inflammation, cell damage and innate immunity could lead to identify new biomarkers of COVID-19 severity, aimed to improve the clinical management of subjects at higher risk of severe outcomes. In a cohort of COVID-19 geriatric patients (n= 156) who required hospitalization we analysed, on-admission, a series of circulating biomarkers related to neutrophil activation (neutrophil elastase, LL-37), macrophage activation (sCD163) and cell damage (nuclear cfDNA, mithocondrial cfDNA and nuclear cfDNA integrity). The above reported biomarkers were tested for their association with in-hospital mortality and with clinical, inflammatory and routine hematological parameters. Aim of the study was to unravel prognostic parameters for risk stratification of COVID-19 patients.
Lower n-cfDNA integrity, higher neutrophil elastase and higher sCD163 levels were significantly associated with an increased risk of in-hospital decease. Median (IQR) values observed in discharged vs. deceased patients were: 0.50 (0.30-0.72) vs. 0.33 (0.22-0.62) for n-cfDNA integrity; 94.0 (47.7-154.0) ng/ml vs. 115.7 (84.2-212.7) ng/ml for neutrophil elastase; 614.0 (370.0-821.0) ng/ml vs. 787.0 (560.0-1304.0) ng/ml for sCD163. The analysis of survival curves in patients stratified for tertiles of each biomarker showed that patients with n-cfDNA integrity < 0.32 or sCD163 in the range 492-811 ng/ml had higher risk of in-hospital decease than, respectively, patients with higher n-cfDNA integrity or lower sCD163. These associations were further confirmed in multivariate models adjusted for age, sex and outcome-related clinical variables. In these models also high levels of neutrophil elastase (>150 ng/ml) appeared to be independent predictor of in-hospital death. An additional analysis of neutrophil elastase in patients stratified for n-cfDNA integrity levels was conducted to better describe the association of the studied parameters with the outcome.
On the whole, biomarkers of cell-free DNA integrity, neutrophil and macrophage activation might provide a valuable contribution to identify geriatric patients with high risk of COVID-19 in-hospital mortality.
Purpose
Zinc (Zn) plays an essential role in many biological processes including immune response. Impaired Zn status promotes immune dysfunction, and it has been associated with enhanced chronic ...inflammation during aging. It has been suggested that the measurement of circulating Zn by itself could not reflect the real Zn status of an individual. It is therefore necessary to identify other determinants associated with plasma Zn to better understanding how physiopathological conditions during aging may affect the concentration of this metal.
Methods
We have investigated the association between Zn levels and some biomarkers in 1090 healthy elderly from five European countries to increase the accuracy in the assessment of the Zn status. Stepwise multivariate linear regression models were used to analyze the influence of factors such as age, dietary intake, inflammatory mediators, laboratory parameters and polymorphisms previously associated with Zn homeostasis.
Results
Plasma Zn decrement was most strongly predicted by age, while positive correlations were found with albumin, RANTES and Zn intake after adjustment for multiple confounders. HSP70 +1267 AA genotype was an independent factor associated with Zn plasma concentrations. Cu/Zn ratio was positively associated with markers of systemic inflammation and age and negatively associated with albumin serum levels.
Conclusions
Our findings show the most important independent determinants of plasma Zn concentration and Cu/Zn ratio variability in elderly population and suggest that the decline with age of Zn circulating levels is more dependent on physiopathological changes occurring with aging rather than to its nutritional intake.
Display omitted
Alzheimer's disease (AD) is the most common age-related neurodegenerative disease. An altered homeostasis of Zinc (Zn) and Copper (Cu), as well as a dysregulated expression of ...Zn-regulatory proteins have been previously described in AD. Acetylcholinesterase inhibitors (AChEI) are commonly used as AD treatment to improve cognitive function, but their effect on Zn homeostasis is still unexplored.
The aims of this study were to define the metal dyshomeostasis in AD patients, to investigate AChEI influence on Zn homeostasis and inflammation, and to analyze the relationship between cognitive impairment at two-year follow-up and metal concentrations, considering AChEI use.
84 Healthy Elderly (HE) and 95 AD patients were enrolled (62 AchEI user and 33 AchEI naïve). HE showed similar plasma Zn and Cu concentrations and Cu/Zn ratio in comparison to AChEI users, but significantly higher Zn level, as well as lower Cu amount and Cu/Zn ratio than AChEI naïve patients. Moreover, AChEI users had increased Zn plasma level, reduced Cu amount, Cu/Zn ratio, and IL1β concentration and lower Zip2 lymphocytic expression vs. naïve patients. A multiple linear regression analysis showed that the MMSE score decline after two-year follow-up was reduced by AChEI therapy and was positively associated with plasma Zn decrease over time.
Our data revealed that AChEI use may affect peripheral Zn and Cu homeostasis in AD patients, decrease Cu/Zn ratio demonstrating a general reduction of inflammatory status in patients under AChEI treatment. Finally, AChEI influence on circulating Zn could be implicated in the drug-related slowdown of cognitive decline.
ZnT8 Arg325Trp polymorphism has been associated with type 2 diabetes (T2DM) susceptibility. The Arg-325 risk variant shows accelerated zinc (Zn) transport kinetic and reduced glucose-stimulated ...insulin secretion in pancreatic cells. However, it remains unexplored the role of Znt8 polymorphism in the regulation of Zn homeostasis and inflammatory response in peripheral blood mononuclear cells (PBMCs) from T2DM patients.
A total of 556 healthy controls and 413 T2DM patients were genotyped for ZnT8 Arg325Trp polymorphism confirming the association of Arg-325 variant with an increased T2DM risk (OR = 1.35 95% C.I: 1.10–1.66; p = 0.0044). Moreover, PBMCs from Arg/Arg T2DM subjects showed increased intracellular free Zn, higher gene expression of Metallothioneins, Znt1, Znt8, Zip2 genes, and reduced Znt4 and Znt7. Higher release of IL-1α, IL-1β, IFN-γ, IL-12p70 and TNF-α and a reduced IL-10 secretion after lipopolysaccharide (LPS) stimulation were observed in PBMCs from Arg/Arg T2DM carriers as compared to subjects with the Trp variant.
Our data provide evidence of a substantial different Zn homeostasis regulation between Znt8 Arg-325 and Trp-325 carriers in PBMCs from T2DM patients. Moreover, Znt8 Arg-325 risk variant shows an enhanced inflammatory response upon LPS stimulation that might aggravate insulin resistance and the progression of diabetes cardiovascular complications.
We present Chandra point-source catalogs for the Extended Chandra Deep Field-South (E-CDF-S) survey. The E-CDF-S consists of four contiguous 250 ks Chandra observations covering an approximately ...square region of total solid angle -0.3 deg super(2), which flank the existing -1 Ms Chandra Deep Field-South (CDF-S). The survey reaches sensitivity limits of -1.1 x 10 super(-16) and -6.7 x 10 super(-16) ergs cm super(-2) s super(-1) for the 0.5-2.0 and 2-8 keV bands, respectively. We detect 762 distinct X-ray point sources within the E-CDF-S exposure; 589 of these sources are new (i.e., not previously detected in the -1 Ms CDF-S). This brings the total number of X-ray point sources detected in the E-CDF-S region to 915 (via the E-CDF-S and -1 Ms CDF-S observations). Source positions are determined using matched-filter and centroiding techniques; the median positional uncertainty is -0.35. The basic X-ray and optical properties of these sources indicate a variety of source types, although absorbed active galactic nuclei (AGNs) seem to dominate. In addition to our main Chandra catalog, we constructed a supplementary source catalog containing 33 lower significance X-ray point sources that have bright optical counterparts (R < 23). These sources generally have X-ray-to-optical flux ratios expected for normal and starburst galaxies, which lack a strong AGN component. We present basic number-count results for our main Chandra catalog and find good agreement with the -1 Ms CDF-S for sources with 0.5-2.0 and 2-8 keV fluxes greater than 3 x 10 super(-16) and 1 x 10 super(-15) ergs cm super(-2) s super(-1), respectively. Furthermore, three extended sources are detected in the 0.5-2.0 keV band, which are found to be likely associated with galaxy groups or poor clusters at z - 0.1-0.7; these have typical rest-frame 0.5-2.0 keV luminosities of (1-5) x 10 super(42) ergs s super(-1).
We studied the X-ray variability of sources detected in the Chandra Deep Field-South, nearly all of which are low- to moderate-z active galactic nuclei (AGNs). We find that 45% of the sources with ...more than 100 counts exhibit significant variability on timescales ranging from a day up to a year. The fraction of sources found to be variable increases with observed flux, suggesting that more than 90% of all AGNs possess intrinsic variability. We also find that the fraction of variable sources appears to decrease with increasing intrinsic absorption; a lack of variability in hard, absorbed AGNs could be due to an increased contribution of reflected X-rays to the total flux. We do not detect significant spectral variability (delta gamma > 0.2) in the majority (approx70%) of our sources. In half of the remaining 30%, the hardness ratio is anticorrelated with flux, mimicking the high/soft-low/hard states of galactic sources. The X-ray variability appears anticorrelated with the luminosity of the sources, in agreement with previous studies. High-redshift sources, however, have larger variability amplitudes than expected from extrapolations of their low-z counterparts, suggesting a possible evolution in the accretion rate and/or size of the X-ray-emitting region. Finally, we discuss some effects that may produce the observed decrease in the fraction of variable sources from z = 0.5 out to z = 2.
PDF
