466 research outputs found

    Immunonutrition before esophagectomy: Impact on immune surveillance mechanisms

    Get PDF
    Preoperative oral immunonutrition was demonstrated to improve immune response and to decrease the infection rate in patients with cancer. This study aimed to assess how immunonutrition could influence the immune cell response in the mucosal microenvironment of esophageal adenocarcinoma. Therefore, A prospective cohort of consecutive patients undergoing esophagectomy for esophageal adenocarcinoma was enrolled. A subgroup of them was given preoperative oral immunonutrition with Oral Impact and was compared to those who received no preoperative supplementation. Mucosal samples from healthy esophagus were obtained at esophagectomy. Histology, immunohistochemistry, gene expression analysis, and cytofluorimetry were performed. Markers of activation of antigen-presenting cells (CD80, CD86, and HLA-I), innate immunity (TLR4 and MyD88), and cytotoxic lymphocyte infiltration and activation (CD8, CD38, CD69, and CD107) were measured. In all, 50 patients received preoperative Oral Impact and 129 patients received no nutritional support. CD80, CD86, MyD88, and CD69 messenger RNA expression was significantly increased in patients receiving immunonutrition compared to controls. In the subgroup of patients with stages I-II cancer, the rate of epithelial cells expressing CD80 and HLA-ABC was significantly higher in those receiving immunonutrition compared to controls as well as CD8+ CD28+ cell rate. Immunonutrition administration before surgery was significantly associated to increased degranulating CD8 and natural killer cells (CD107+) infiltrating the healthy esophageal mucosa. All the comparisons were adjusted for cancer stage and preoperative therapy. In conclusion, in healthy esophageal mucosa of patients undergoing esophagectomy, a 5-day course of immunonutrition enhances expression of antigen-presenting cells activity and increased CD8+ T cell activation and degranulating activity. Further studies are warranted to understand the clinical implication in terms of cancer recurrence

    Unimolecular Variant of the Fluorescence Turn-On Oxidative Coupling of Catecholamines with Resorcinols

    Get PDF
    Reported herein is a unimolecular variant of the fluorescence turn-on oxidative coupling of catecholamines with resorcinols ("FluoResCat") based on the easily accessible conjugate 4-(2-((2,4-dihydroxybenzyl)amino)ethyl)benzene-1,2-diol (1). The process involves an alkali-activatable sequence of autoxidation and intramolecular cyclization steps with loss of carbon, leading to a fluorescent methanobenzofuroazocinone product identical to that obtained from the oxidative coupling of dopamine with resorcinol. A mechanistic route for this unexpected reaction, mimicking the synthesis of the natural fluorophore matlaline, would involve highly constrained polycyclic spiro intermediates (liquid chromatography–mass spectrometry analysis of intermediates, model reactions, and density functional theory calculations). Emission turn-on from 1 in response to oxygen, superoxide-generating systems, or gaseous ammonia/volatile amines may be of interest for sensing applications, for example, in smart packaging

    Development of a novel, compact, and transportable multispectral imaging device for wound healing monitoring

    Get PDF
    Multispectral imaging (MSI) devices are optical diagnostic tools that can be used for the non-invasive monitoring and characterization of various kinds of pathologies, including skin conditions such as wounds and ulcers, due to the capability of such technology to track alterations of structural and physiological parameters (e.g., oxygenation and haemodynamics) from changes in the optical properties of the investigated tissue across a large number of spectral bands. In this work, a novel, compact and transportable MSI device based on spectral scanning and diffuse reflectance imaging is going to be presented. The apparatus is composed of light emitting diodes (LEDs) as light sources and a CMOS camera, making it a very compact, manageable, user-friendly, and cost-effective system. The wavelengths of the LED sources, that are located in the visible-NIR portion of the spectrum, have been specifically selected to target and monitor alterations of oxygenation and haemodynamics that can provide biomarkers of monitoring wound healing in chronic ulcers. The calibration of the MSI system is going to be illustrated, discussing the calibration procedure and results obtained with (1) Monte Carlo-based, digital phantoms and (2) liquid optical phantoms. Both types of phantoms mimic the properties of biological tissues and allow to introduce variations in a controlled manner. The proposed MSI system is also going to be tested on patients affected by chronic skin ulcers in order to assess its efficacy and accuracy

    A complete set-up to evaluate the correlation between blood pressure and pulse transit time

    Get PDF
    Blood pressure (BP) has always been one of the most important parameters in monitoring cardiovascular system conditions and coronary artery diseases (CAD), such as angina and myocardial infarction (commonly known as a heart attack). This is due to the fact that many of the changes within the cardiovascular system, such as clogged arteries, for example, are reflected by changes in BP. A number of methods and devices that can measure BP are available on the market for both clinical and consumer use. However, being able to measure one’s own BP non-invasively, with the required frequency (even continuously) in a comfortable fashion remains an unsolved problem using currently available systems. To date, the Pulse Transit Time (PTT) measurement method has been seen as a feasible approach to help bring current blood pressure monitoring systems to a stage where non-invasive, continuous measurements are viable. However, developing a system which uses the PTT method for blood pressure measurement is as yet an unsolved problem and it remains a challenge to achieve accurate BP results despite considerable research in the past decade. In this paper, we present the first step in building a smart sensing system that overcomes the technical difficulties associated with accurate measurement of PTT. The novel hardware developed incorporates multi-modal sensing capability to explore and quantify the relationship between blood pressure and PTT. The evaluation system is completed by efficient, simple and fast embedded software algorithms, user interface, and clinical validation trials that will enable delivering a novel PTT-based blood pressure monitor

    Towards a systems biology approach to mammalian cell cycle: modeling the entrance into S phase of quiescent fibroblasts after serum stimulation

    Get PDF
    Background: The cell cycle is a complex process that allows eukaryotic cells to replicate chromosomal DNA and partition it into two daughter cells. A relevant regulatory step is in the G0/G1phase, a point called the restriction (R) point where intracellular and extracellular signals are monitored and integrated. Results: Subcellular localization of cell cycle proteins is increasingly recognized as a major factor that regulates cell cycle transitions. Nevertheless, current mathematical models of the G1/S networks of mammalian cells do not consider this aspect. Hence, there is a need for a computational model that incorporates this regulatory aspect that has a relevant role in cancer, since altered localization of key cell cycle players, notably of inhibitors of cyclin-dependent kinases, has been reported to occur in neoplastic cells and to be linked to cancer aggressiveness. Conclusion: The network of the model components involved in the G1to S transition process was identified through a literature and web-based data mining and the corresponding wiring diagram of the G1to S transition drawn with Cell Designer notation. The model has been implemented in Mathematica using Ordinary Differential Equations. Time-courses of level and of sub-cellular localization of key cell cycle players in mouse fibroblasts re-entering the cell cycle after serum starvation/re-feeding have been used to constrain network design and parameter determination. The model allows to recapitulate events from growth factor stimulation to the onset of S phase. The R point estimated by simulation is consistent with the R point experimentally determined. The major element of novelty of our model of the G1to S transition is the explicit modeling of cytoplasmic/nuclear shuttling of cyclins, cyclin-dependent kinases, their inhibitor and complexes. Sensitivity analysis of the network performance newly reveals that the biological effect brought about by Cki overexpression is strictly dependent on whether the Cki is promoting nuclear translocation of cyclin/Cdk containing complexes. © 2009 Alfieri et al; licensee BioMed Central Ltd

    Changes in meteo-hydrological extremes in Spain at different levels of global warming

    Get PDF
    Ponencia presentada en: XI Congreso de la Asociación Española de Climatología celebrado en Cartagena entre el 17 y el 19 de octubre de 2018.This work assesses changes in the extremes of precipitation and streamflow in Spain assuming global warming scenarios of 1.5, 2, and 3 degrees Celsius from pre-industrial levels. We consider an ensemble of seven regional climate model simulations spanning the period 1970-2099 to evaluate precipitation changes and to drive a distributed hydrological model and thus to derive streamflow statistics under present and future climates. The climate simulations were performed under the umbrella of the EURO-CORDEX project, thus covering Europe with a spatial resolution of 0.11 degree both in latitude and longitude, the finest so far in this type of climatological multimodel and multi-scenario experiments. Preliminary results suggest that constraining global warming well below 2°C, as sought in the Paris Agreement, reduces the probability of increasing drought related indices.This work has been supported by the Spanish Projects HOPE (CGL2014-52571-R) and M-CostAdapt (CTM2017-83655-C2-2-R) of the Ministry of Economy, Industry and Competitiveness, as well as the EFA 210/216 PIRAGUA project financed by the INTERREG V A (POCTEFA) and FEDER

    Ceftazidime-Avibactam Combination Therapy Compared to Ceftazidime-Avibactam Monotherapy for the Treatment of Severe Infections Due to Carbapenem-Resistant Pathogens: A Systematic Review and Network Meta-Analysis

    Get PDF
    Ceftazidime-avibactam (CZA) is a novel beta-lactam beta-lactamase inhibitor combination approved for the treatment of complicated urinary tract infections, complicated intra-abdominal infections, and for hospital-acquired/ventilator-associated pneumonia. The aim of this systematic review (PROSPERO registration number: CRD42019128927) was to evaluate the effectiveness of CZA combination therapy versus CZA monotherapy in the treatment of severe infections. The databases included in the search, until February 12th, 2020, were MEDLINE by PubMed, EMBASE, and The Cochrane Central Register of Controlled Trials. We included both randomized controlled trials (RCTs) and non-randomized studies published in peer-reviewed journals and in the English language. The primary outcome was all-cause mortality (longest follow-up) evaluated in patients with the diagnosis of infection with at least one pathogen; secondary outcomes were clinical and microbiological improvement/cure. Thirteen studies were included in the qualitative synthesis: 7 RCTs and 6 retrospective studies All the six retrospective studies identified carbapenamase-producing Enterobacteriaceae (CRE) as the cause of infection and for this reason were included in the network meta-analysis (NMA); the quality of the studies, assessed using the New Castle-Ottawa Scale, was moderate-high. In all the six retrospective studies included in the NMA, CZA was used in large part for off-label indications (mostly blood stream infections: 80-100% of patients included). No difference in mortality rate was observed in patients undergoing CZA combination therapy compared to CZA monotherapy [n = 503 patients, direct evidence OR: 0.96, 95% CI: 0.65-1.41]

    Changes in flood damage with global warming on the eastern coast of Spain

    Get PDF
    Flooding is one of the main natural hazards in the world and causes huge economic and human impacts. Assessing the flood damage in the Mediterranean region is of great importance, especially because of its large vulnerability to climate change. Most past floods affecting the region were caused by intense precipitation events; thus the analysis of the links between precipitation and flood damage is crucial. The main objective of this paper is to estimate changes in the probability of damaging flood events with global warming of 1.5, 2 and 3¿°C above pre-industrial levels and taking into account different socioeconomic scenarios in two western Mediterranean regions, namely Catalonia and the Valencian Community. To do this, we analyse the relationship between heavy precipitation and flood-damage estimates from insurance datasets in those two regions. We consider an ensemble of seven regional climate model (RCM) simulations spanning the period 1976–2100 to evaluate precipitation changes and to drive a logistic model that links precipitation and flood-damage estimates, thus deriving statistics under present and future climates. Furthermore, we incorporate population projections based on five different socioeconomic scenarios. The results show a general increase in the probability of a damaging event for most of the cases and in both regions of study, with larger increments when higher warming is considered. Moreover, this increase is higher when both climate and population change are included. When population is considered, all the periods and models show a clearly higher increase in the probability of damaging events, which is statistically significant for most of the cases. Our findings highlight the need for limiting global warming as much as possible as well as the importance of including variables that consider change in both climate and socioeconomic conditions in the analysis of flood damage.Peer ReviewedPostprint (published version
    corecore