Features of postoperative immune suppression are reversible with interferon gamma and independent of interleukin-6 pathways

OBJECTIVE The aim of this study was to evaluate the role of interleukin (IL)-6 pathways in postoperative immune suppression and to assess the reversibility of this phenomenon. BACKGROUND The postoperative period is characterized by increased IL-6 production and features of immune suppression. In vitro, IL-6 mediates anti-inflammatory effects through inhibition of interferon gamma (IFN-γ) pathways. The significance of the immunomodulatory effects of IL-6 in the clinical setting of postoperative immune suppression remains unclear. METHODS Patients over 45 years old undergoing elective surgery, involving the gastrointestinal tract, were recruited. IL-6 levels were assayed using an enzyme linked immunosorbent assay preoperatively, and at 24 and 48 hours. Peripheral blood mononuclear cells from healthy volunteers were cultured in perioperative serum and CD14Human Leukocyte Antigen-DR (HLA-DR) [monocyte HLA-DR (mHLA-DR)] geometric mean florescent intensity was measured in the presence and absence of IL-6 neutralizing antibody and recombinant IFN-γ. RESULTS Of the 108 patients, 41 developed a postoperative infection. The IL-6 levels increased 19-fold from the preoperative sample to 24 hours postoperatively (P < 0.0001). Higher IL-6 levels at 24 (P = 0.0002) and 48 hours (P = 0.003) were associated with subsequent postoperative infectious complications. mHLA-DR mean florescent intensity fell when healthy peripheral blood mononuclear cells were cultured with postoperative serum compared with preoperative serum (P = 0.008). This decrease was prevented by the presence of IFN-γ in the culture media, but not by the presence of IL-6-neutralizing antibody. CONCLUSIONS IL-6 levels increase after a major surgery and are associated with an increased susceptibility to postoperative infections. Serum obtained from postoperative patients induces an immunosuppressive response, reflected in reduced mHLA-DR levels, mediated through IL-6 independent pathways and is reversible with IFN-γ. These data may have therapeutic implications for the prevention of infection in patients undergoing major surgery

Perioperative blood transfusion is associated with a gene transcription profile characteristic of immunosuppression: a prospective cohort study

INTRODUCTION Blood transfusion in the perioperative period has frequently been associated with an excess of nosocomial infections. Whilst transfused whole blood induces specific host immune alteration that may predispose to nosocomial infections, the immunomodulating properties associated with leukodepleted blood remain incompletely understood. In this study, we explore the hypothesis that the transfusion of leukodepleted allogeneic blood during or following major gastrointestinal surgery is associated with an immunosuppressed phenotype, which may in turn predispose to postoperative infectious complications. METHODS Patients aged over 45 years undergoing scheduled inpatient major gastrointestinal surgery were recruited. Gene expression profiles of specific inflammatory genes were assayed from blood collected preoperatively, at 24 and at 48 hours after surgery. Genes were selected based on their ability to represent specific immune pathways. Gene expression was quantified using quantitative real-time polymerase chain reaction (qRT-PCR) to measure messenger RNA (mRNA) levels. Postoperative infections were documented using predefined criteria. RESULTS One hundred and nineteen patients were recruited. Fifteen (13%) patients required blood transfusion within 24 hours of surgery, 44 (37%) patients developed infections and 3 (2%) patients died prior to discharge. Patients receiving a blood transfusion were more likely to develop postoperative infections (P =0.02) and to have lower tumour necrosis factor alpha (TNFα), interleukin (IL)-12, IL-23 and RAR-related orphan receptor gamma T (RORγt) gene expression in the postoperative period (P <0.05). The TNFα/IL-10 mRNA ratio at 24 hours (P =0.0006) and at 48 hours (P =0.01) was lower in patients receiving a blood transfusion over this period. Multivariable analysis confirmed that these observations were independent of the severity of the surgical insult. CONCLUSIONS An association between an immunosuppressive pattern of gene expression and blood transfusion following major elective gastrointestinal surgery is described. This gene expression profile includes a reduction in the activity of innate immunity and T helper cell type 1 (Th1) and T helper cell type 17 (Th17) pathways in those patients receiving a blood transfusion. Blood transfusion was also associated with an excess of infectious complications in this cohort. A mechanistic link is suggested but not proven

Leverage web analytics for real time website browsing recommendations

Trabalho apresentado no 5th World Conference on Information Systems and Technologies (WorldCIST’17), 11-13 de abril 2017, Porto Santo, Madeira PortugalAs a websites’ structure grow it is paramount to accommodate the alignment of user needs and experience with the overall websites’ purposes. Toward this requirement, the proposed website navigation recommendation system suggests to users, pages that might be of her interest based on past successful navigation patterns of overall site’s usage. Most of existing recommendation systems adopts traditionally one of the web mining branches. We take a different stance, on web mining usage, and alternatively considered the real time enactment of web analytic tools supported analysis given their current maturity and affordances. On this basis we provide a model, its implementation and evaluation for navigation based recommendations generation and delivery. The developed prototype adopted a SaaS orientation to promote the underlying functionalities integration within any website. Preliminary evaluation’s results seem to favor the validation of the present contribution rational.N/

Improvements in electrochemical glucose biosensors

Diabetes is one of the leading causes of death and disability in the world. Even though insulin was discovered in 1920, an intense research on diabetes has been conducted during the last five decades and this is because of the market size. The huge demand is creating the need for the development of new approaches. This project involved the research aimed at better understanding and improvements in performance of glucose biosensors. In general, high surface area electrodes are desired as the high surface area provides more active sites for electrochemical reactions, and hence higher kinetic rate capability. Therefore, the determination of the active electrochemical surface area of the electrode is very important. A study has been conducted to determine the real electrochemical surface area of the Pelikan screen printed electrodes (SPEs) and a method has been optimised and established by Pelikan for the evaluation of their SPEs. Another very important issue that most of the current blood glucose monitoring tests are facing is the haematocrit effect, since the haematocrit differences observed in the blood samples can significantly affect glucose measurements. Therefore a study has been conducted in order to observe the absorption of the blood samples into the working electrode paste according to the haematocrit level. The second part of the study included the characterisation of the novel conjugated polymer made of N-(N, N’ diethyldicarbamoyl ethyl amido ethyl) aniline (NDDEAEA), the optimization of the conditions for the electrochemical polymerization, their application in grafting and finally the development of NDDEAEA based glucose biosensor. The new conducting polymer, acted as a matrix for the biosensor fabrication in this study, possesses macroiniferter properties and is capable of initiation free radical initiated addition polymerisation after formation of the polyaniline (PANI) material while preserving or even enhancing some of the PANI’s electrochemical properties. This material can potentially be used in the construction of novel Pelikan electrodes with enhanced integration functionalities, e.g. grafting non adhesive polymer coatings to assure that the poor performance in sensors as a result of impact of blood components can be mitigated. The final study included the development and optimisation of the reaction conditions for grafting a hyperbranched polymer onto the surface of the multi walled carbon nanotubes (MWCNT), using the A3 and B2 approach (described below). The aim of this work was achieving further increase in the sensitivity of Pelikan sensors.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Deep optical study of the mixed-morphology supernova remnant G 132.7+1.3 (HB3)

We present optical CCD images of the large supernova remnant (SNR) G 132.7+1.3 (HB3) covering its full extent for the first time, in the emission lines of Hα +[N II], [S II], and [O III], where new and known filamentary and diffuse structures are detected. These observations are supplemented by new low-resolution long-slit spectra and higher resolution images in the same emission lines. Both the flux-calibrated images and spectra confirm that the optical emission originates from shock-heated gas since the [S II]/Hα > 0.4. Our findings are also consistent with the recently developed emission-line ratio diagnostics for distinguishing SNRs from H II regions. A multiwavelength comparison among our optical data and relevant observations in radio, X-rays, gamma-rays and CO bands, provided additional evidence on the interaction of HB3 with the surrounding clouds and clarified the borders of the SNR and the adjacent cloud. We discuss the supernova (SN) properties and evolution that led to the current observables of HB3 and we show that the remnant has most likely passed at the pressure driven snowplow phase. The estimated SN energy was found to be (3.7 ± 1.5) × 1051 erg and the current SNR age (5.1 ± 2.1) × 104 yr. We present an alternative scenario according to which the SNR evolved in the wind bubble cavity excavated by the progenitor star and currently is interacting with its density walls. We show that the overall mixed morphology properties of HB3 can be explained if the SN resulted by a Wolf−Rayet progenitor star with mass ∼34 M⊙⁠

Risk of stroke in hospitalized SARS-CoV-2 infected patients: A multinational study

Background: There is an increased attention to stroke following SARS-CoV-2. The goal of this study was to better depict the short-term risk of stroke and its associated factors among SARS-CoV-2 hospitalized patients. Methods: This multicentre, multinational observational study includes hospitalized SARS-CoV-2 patients from North and South America (United States, Canada, and Brazil), Europe (Greece, Italy, Finland, and Turkey), Asia (Lebanon, Iran, and India), and Oceania (New Zealand). The outcome was the risk of subsequent stroke. Centres were included by non-probability sampling. The counts and clinical characteristics including laboratory findings and imaging of the patients with and without a subsequent stroke were recorded according to a predefined protocol. Quality, risk of bias, and heterogeneity assessments were conducted according to ROBINS-E and Cochrane Q-test. The risk of subsequent stroke was estimated through meta-analyses with random effect models. Bivariate logistic regression was used to determine the parameters with predictive outcome value. The study was reported according to the STROBE, MOOSE, and EQUATOR guidelines. Findings: We received data from 26,175 hospitalized SARS-CoV-2 patients from 99 tertiary centres in 65 regions of 11 countries until May 1st, 2020. A total of 17,799 patients were included in meta-analyses. Among them, 156(0.9) patients had a stroke�123(79) ischaemic stroke, 27(17) intracerebral/subarachnoid hemorrhage, and 6(4) cerebral sinus thrombosis. Subsequent stroke risks calculated with meta-analyses, under low to moderate heterogeneity, were 0.5 among all centres in all countries, and 0.7 among countries with higher health expenditures. The need for mechanical ventilation (OR: 1.9, 95 CI:1.1�3.5, p = 0.03) and the presence of ischaemic heart disease (OR: 2.5, 95 CI:1.4�4.7, p = 0.006) were predictive of stroke. Interpretation: The results of this multi-national study on hospitalized patients with SARS-CoV-2 infection indicated an overall stroke risk of 0.5(pooled risk: 0.9). The need for mechanical ventilation and the history of ischaemic heart disease are the independent predictors of stroke among SARS-CoV-2 patients. Funding: None. © 2020 The Author