The nature of the unresolved extragalactic soft CXB

In this paper we investigate the power spectrum of the unresolved 0.5-2 keV CXB with deep Chandra 4 Ms observations in the CDFS. We measured a signal which, on scales >30", is significantly higher than the Shot-Noise and is increasing with the angular scale. We interpreted this signal as the joint contribution of clustered undetected sources like AGN, Galaxies and Inter-Galactic-Medium (IGM). The power of unresolved cosmic sources fluctuations accounts for \sim 12% of the 0.5-2 keV extragalactic CXB. Overall, our modeling predicts that \sim 20% of the unresolved CXB flux is made by low luminosity AGN, \sim 25% by galaxies and \sim 55% by the IGM (Inter Galactic Medium). We do not find any direct evidence of the so called Warm Hot Intergalactic Medium (i.e. matter with 10^5K<T<10^7K and density contrast {\delta} <1000), but we estimated that it could produce about 1/7 of the unresolved CXB. We placed an upper limit to the space density of postulated X-ray-emitting early black hole at z>7.5 and compared it with SMBH evolution models.Comment: 15 pages, 9 figures, accepted by MNRA

Intraoperative blood pressure changes as a risk factor for anastomotic leakage in colorectal surgery

Anastomotic leakage is a serious complication after colorectal surgery. Pre- and intraoperative factors may contribute to failure of colorectal anastomosis. In this study we have tried to determine risk factors for anastomotic leakage, with special emphasis on intraoperative blood pressure changes. During a 24-month period, patients receiving a colorectal anastomosis were prospectively evaluated. For each patient preoperative characteristics, intraoperative adverse events and surgical outcome data were collected. Blood pressure changes were calculated as a relative decrease (> 25% and > 40%) from preoperative baseline values. During the study period, 285 patients underwent colorectal surgery with an anastomosis. Fifteen patients developed an anastomotic leakage (5.3%). All patients who developed a leakage had a left-sided procedure (P 40% decrease in diastolic blood pressure (P = 0.049)] were identified as univariate risk factors for anastomotic leakage. The development of an anastomotic leakage after colorectal surgery is related to surgical, patient and anaesthetic risk factors. A high preoperative diastolic blood pressure and profound intraoperative hypotension combined with complex surgery, marked by a blood loss of a parts per thousand yen250 mL and the occurrence of intraoperative adverse events, is associated with an increased risk of developing anastomotic leakag

Tracing the cosmic growth of supermassive black holes to z~3 with Herschel

We study a sample of Herschel selected galaxies within the Great Observatories Origins Deep Survey-South and the Cosmic Evolution Survey fields in the framework of the Photodetector Array Camera and Spectrometer (PACS) Evolutionary Probe project. Starting from the rich multiwavelength photometric data sets available in both fields, we perform a broad-band spectral energy distribution decomposition to disentangle the possible active galactic nucleus (AGN) contribution from that related to the host galaxy. We find that 37 per cent of the Herschel-selected sample shows signatures of nuclear activity at the 99 per cent confidence level. The probability of revealing AGN activity increases for bright (L 1−1000 > 10 11 L ? ) star-forming galaxies at z > 0.3, becoming about 80 per cent for the brightest (L 1−1000 > 10 12 L ? ) Infrared (IR) galaxies at z≥1. Finally, we reconstruct the AGN bolometric luminosity function and the supermassive black hole growth rate across cosmic time up to z ∼ 3 from a far-IR perspective. This work shows general agreement with most of the panchromatic estimates from the literature, with the global black hole growth peaking at z ∼ 2 and reproducing the observed local black hole mass density with consistent values of the radiative efficiency Erad (∼0.07)

A stable aberrant immunophenotype characterizes nearly all cases of cutaneous T-cell lymphoma in blood and can be used to monitor response to therapy

BACKGROUND: Abnormal variations in the expression level of some commonly expressed T-cell antigens are a feature of many T-cell malignancies. METHODS: We sought to assess the frequency of such abnormal antigen expression by flow cytometry in peripheral blood (PB) samples from patients with mycosis fungoides (MF) and Sézary syndrome (SS). We correlated presence of morphologically identifiable tumor cells on PB smear with the frequency of abnormalities in the level of expression of CD3, CD4, CD7, CD8 and CD26. We also examined the degree of stability of these abnormal findings in tumor cells over the course of disease. The flow cytometric findings in 100 PB samples from 44 patients, including 38 who had multiple sequential PB samples (2–8 samples each), were assessed. RESULTS: Abnormalities were seen in the expression level of one or more T-cell markers in 41 cases (93%) including CD3 in 34% of patients, CD4 in 54%, CD26 in 86% and CD 45 in 40% (10 cases tested). In all but 2 cases, the abnormal T-cell immunophenotype remained similar over the course of treatment and correlated with the relative numbers of tumor cells counted on PB smear. CONCLUSIONS: Using a standard T-cell panel, stable phenotypically aberrant T-cell populations representing the tumor are detected in the vast majority of involved PB samples in MF/SS and can be used to monitor response to therapy

Anti-HIV Activity Mediated by Natural Killer and CD8+ Cells after Toll-Like Receptor 7/8 Triggering

We previously found that triggering TLR7/8 either by single stranded HIV RNA or synthetic compounds induced changes in the lymphoid microenvironment unfavorable to HIV. In this study, we used selective TLR7 and 8 agonists to dissect their contribution to the anti-HIV effects. While triggering TLR7 inhibited efficiently HIV replication in lymphoid suspension cells from tonsillar origin, its effect was inconsistent in peripheral blood mononuclear cells (PBMC). In contrast, triggering TLR8 showed a very prominent and overall very consistent effect in PBMC and tonsillar lymphoid suspension cells. Depletion of dendritic cells (DC), Natural killer cells (NK) and CD8+ T-cells from PBMC resulted in the reversal of TLR8 induced anti-HIV effects. Especially noteworthy, depletion of either NK or CD8+ T-cells alone was only partially effective. We interpret these findings that DC are the initiator of complex changes in the microenvironment that culminates in the anti-HIV active NK and CD8+ effector cells. The near lack of NK and the low number of CD8+ T-cells in tonsillar lymphoid suspension cells may explain the lower TLR8 agonist's anti-HIV effects in that tissue. However, additional cell-type specific differences must exist since the TLR7 agonists had a very strong inhibitory effect in tonsillar lymphoid suspension cells. Separation of effector from the CD4+ target cells did not abolish the anti-HIV effects pointing to the critical role of soluble factors. Triggering TLR7 or 8 were accompanied by major changes in the cytokine milieu; however, it appeared that not a single soluble factor could be assigned for the potent effects

Elevated Serum Uric Acid Is Associated with High Circulating Inflammatory Cytokines in the Population-Based Colaus Study

BACKGROUND: The relation of serum uric acid (SUA) with systemic inflammation has been little explored in humans and results have been inconsistent. We analyzed the association between SUA and circulating levels of interleukin-6 (IL-6), interleukin-1beta (IL-1beta), tumor necrosis factor- alpha (TNF-alpha) and C-reactive protein (CRP). METHODS AND FINDINGS: This cross-sectional population-based study conducted in Lausanne, Switzerland, included 6085 participants aged 35 to 75 years. SUA was measured using uricase-PAP method. Plasma TNF-alpha, IL-1beta and IL-6 were measured by a multiplexed particle-based flow cytometric assay and hs-CRP by an immunometric assay. The median levels of SUA, IL-6, TNF-alpha, CRP and IL-1beta were 355 micromol/L, 1.46 pg/mL, 3.04 pg/mL, 1.2 mg/L and 0.34 pg/mL in men and 262 micromol/L, 1.21 pg/mL, 2.74 pg/mL, 1.3 mg/L and 0.45 pg/mL in women, respectively. SUA correlated positively with IL-6, TNF-alpha and CRP and negatively with IL-1beta (Spearman r: 0.04, 0.07, 0.20 and 0.05 in men, and 0.09, 0.13, 0.30 and 0.07 in women, respectively, P&lt;0.05). In multivariable analyses, SUA was associated positively with CRP (beta coefficient +/- SE = 0.35+/-0.02, P&lt;0.001), TNF-alpha (0.08+/-0.02, P&lt;0.001) and IL-6 (0.10+/-0.03, P&lt;0.001), and negatively with IL-1beta (-0.07+/-0.03, P = 0.027). Upon further adjustment for body mass index, these associations were substantially attenuated. CONCLUSIONS: SUA was associated positively with IL-6, CRP and TNF-alpha and negatively with IL-1beta, particularly in women. These results suggest that uric acid contributes to systemic inflammation in humans and are in line with experimental data showing that uric acid triggers sterile inflammation

Excretory/Secretory-Products of Echinococcus multilocularis Larvae Induce Apoptosis and Tolerogenic Properties in Dendritic Cells In Vitro

Parasitic helminths are inducers of chronic diseases and have evolved mechanisms to suppress the host immune response. Mostly from studies on roundworms, a picture is currently emerging that helminths secrete factors (E/S-products) that directly act on sentinels of the immune system, dendritic cells, in order to achieve an expansion of immunosuppressive, regulatory T cells (T-reg). Parasitic helminths are currently also intensely studied as therapeutic agents against autoimmune diseases and allergies, which is directly linked to their immunosuppressive activities. The immunomodulatory products of parasitic helminths are therefore of high interest for understanding immunopathology during infections and for the treatment of allergies. The present work was conducted on larvae of the tapeworm E. multilocularis, which grow like a tumor into surrounding host tissue and thus cause the lethal disease alveolar echinococcosis. The authors found that E/S-products from early infective larvae are strong inducers of tolerogenic DC in vitro and show that E/S-products of larvae of the chronic stage lead to an in vitro expansion of Foxp3+ T cells, suggesting that both the expansion of these T cells and poorly responsive DC are important for the establishment and persistence of E. multilocularis larvae within the host

Phenotypic and Functional Properties of Helios+ Regulatory T Cells

Helios, an Ikaros family transcription factor, is preferentially expressed at the mRNA and protein level in regulatory T cells. Helios expression previously appeared to be restricted to thymic-derived Treg. Consistent with recent data, we show here that Helios expression is inducible in vitro under certain conditions. To understand phenotypic and functional differences between Helios+ and Helios− Treg, we profiled cell-surface markers of FoxP3+ Treg using unmanipulated splenocytes. We found that CD103 and GITR are expressed at high levels on a subset of Helios+ Treg and that a Helios+ Treg population could be significantly enriched by FACS sorting using these two markers. Quantitative real-time PCR (qPCR) analysis revealed increased TGF-β message in Helios+ Treg, consistent with the possibility that this population possesses enhanced regulatory potential. In tumor-bearing mice, we found that Helios+ Treg were relatively over-represented in the tumor-mass, and BrdU studies showed that, in vivo, Helios+ Treg proliferated more than Helios− Treg. We hypothesized that Helios-enriched Treg might exert increased suppressive effects. Using in vitro suppression assays, we show that Treg function correlates with the absolute number of Helios+ cells in culture. Taken together, these data show that Helios+ Treg represent a functional subset with associated CD103 and GITR expression

Levels and Determinants of Inflammatory Biomarkers in a Swiss Population-Based Sample (CoLaus Study)

OBJECTIVE: to assess the levels and determinants of interleukin (IL)-1β, IL-6, tumour necrosis factor (TNF)-α and C-reactive protein (CRP) in a healthy Caucasian population. METHODS: population sample of 2884 men and 3201 women aged 35 to 75. IL-1β, IL-6 and TNF-α were assessed by a multiplexed particle-based flow cytometric assay and CRP by an immunometric assay. RESULTS: Spearman rank correlations between duplicate cytokine measurements (N = 80) ranged between 0.89 and 0.96; intra-class correlation coefficients ranged between 0.94 and 0.97, indicating good reproducibility. Among the 6085 participants, 2289 (37.6%), 451 (7.4%) and 43 (0.7%) had IL-1β, IL-6 and TNF-α levels below detection limits, respectively. Median (interquartile range) for participants with detectable values were 1.17 (0.48-3.90) pg/ml for IL-1β; 1.47 (0.71-3.53) pg/ml for IL-6; 2.89 (1.82-4.53) pg/ml for TNF-α and 1.3 (0.6-2.7) ng/ml for CRP. On multivariate analysis, greater age was the only factor inversely associated with IL-1β levels. Male sex, increased BMI and smoking were associated with greater IL-6 levels, while no relationship was found for age and leisure-time PA. Male sex, greater age, increased BMI and current smoking were associated with greater TNF-α levels, while no relationship was found with leisure-time PA. CRP levels were positively related to age, BMI and smoking, and inversely to male sex and physical activity. CONCLUSION: Population-based levels of several cytokines were established. Increased age and BMI, and to a lesser degree sex and smoking, significantly and differentially impact cytokine levels, while leisure-time physical activity has little effect