The role of Lactoferrin in intestinal health

The intestine represents one of the first barriers where microorganisms and environmental antigens come into tight contact with the host immune system. A healthy intestine is essential for the well-being of humans and animals. The period after birth is a very important phase of development, as the infant moves from a protected environment in the uterus to one with many of unknown antigens and pathogens. In that period, mother’s milk plays an important role, as it contains an abundance of biologically active components. Among these components, the iron-binding glycoprotein, lactoferrin (LF), has demonstrated a variety of important benefits in infants and adults, including the promotion of intestinal health. This review article aims to provide a compilation of all the information related to LF and intestinal health, in infants and adults

Whey and Buttermilk-Based Formulas Modulate Gut Microbiota in Mice with Antibiotic-Induced Dysbiosis

ScopeDiet is one of the main factors that modifies intestinal microbiota composition. The search for foods that can reverse situations of intestinal dysbiosis such as that induced by antibiotics is of great interest. Buttermilk and whey are the main by‐products produced by the dairy industry containing bioactive compounds. The aim of this study is to investigate the ability of whey and buttermilk‐based formulas supplemented with lactoferrin and milk fat globule membrane (MFGM) to modulate the effects of clindamycin on mouse intestinal microbiota.Methods and resultsMale C57BL/6 mice are treated with saline (control), clindamycin (Clin), a formula containing whey (F1) or buttermilk (F2), Clin+F1 or Clin+F2, and their fecal microbiota profiles are analyzed by sequencing of 16S rRNA gene using the MinION device. Clin induces alterations in both the composition and metabolic functions of the mice intestinal microbiota. The treatment with F1 or F2 reverses the effects of clindamycin, restoring the levels of Rikenellaceae and Lactobacillaceae families and certain pathways related to short‐chain fatty acids production and tetrahydrofolate biosynthesis.ConclusionWhey and buttermilk supplemented with lactoferrin and MFGM may be a bioactive formula for functional foods to prevent or restore microbiota alterations induced by antibiotic administration

Comparative effect of bovine buttermilk, whey, and lactoferrin on the innate immunity receptors and oxidative status of intestinal epithelial cells

Milk contains active molecules with important functional properties as the defensive proteins; among them are the whey protein lactoferrin and proteins of the milk fat globule membrane (MFGM) present in buttermilk. The aim of this study has been to investigate the effect of lactoferrin, whey and buttermilk as modulators of intestinal innate immunity and oxidative stress on intestinal epithelial cells, to evaluate its potential use for the development of functional foods. Innate immune Toll-like receptors (TLR2, TLR4, and TLR9) mRNA expression, lipid peroxidation (MDA+4-HDA) and protein carbonyl levels were analyzed in enterocyte-like Caco-2/TC7 cells treated for 24 hours with different concentrations of lactoferrin, whey or buttermilk. None of the substances analyzed caused oxidative damage; however, whey significantly decreased the levels of lipid peroxidation. Furthermore, both lactoferrin and whey were able to reduce the oxidative stress induced by lipopolysaccharide. Respect to TLR receptors, lactoferrin, whey and buttermilk specifically altered the expression of TLR2, TLR4 and TLR9 receptors, with a strong decrease in TLR4 expression. These results suggest that lactoferrin, whey and buttermilk could be interesting potential ingredients for functional foods as they seem to modulate oxidative stress and inflammatory response induced by TLRs activation

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Multi-Sensor Data Fusion for High-Precision Indoor/Outdoor UAV Navigation

El juny de 2015, la Comissió Europea va decidir invertir en el desenvolupament d’un nou projecte de recerca anomenat TIMON, incl òs dins del programa Horizon 2020. El principal objectiu d’aquest projecte europeu consisteix en establir un sistema cooperatiu on persones, vehicles i infraestructures estiguin tots connectats entre ells. Amb TIMON es pret én elevar els est àndards de seguretat, eficiència i flexibilitat dels sistemes de transport terrestre. Part d’aquest projecte s’ha realitzat al Centre Tecnològic de Telecomunicacions de Catalunya (CTTC), el qual és el responsable de la creaci ó d’una plataforma de posicionament que porta integrades dues Unitats de Mesura Inercial (IMU en anglès) ajudades per un Sistema de Navegació Global per Sat` el lit (GNSS en angl` es). Tot aix ò s’ha preparat amb la finalitat de proporcionar posicionament de manera precisa i completament fiable. Els objectius generals d’aquesta tesis són: i) contribuir a la plataforma de TIMON per tal de millorar la navegació en vehicles terrestres i, conseq¨uentment, obtenir millors resultats de posici ó en zones on la recepció de senyals GPS és molt d` ebil or nul la i els Sistemes de Navegació Inercial (INS en anglès) de baix cost no són capac¸os de garantir una navegació per estima de qualitat; i ii) estendre l’ ús d’aquesta plataforma per poder ser aplicada a Vehicles Sense Pilot (UAV en angl` es), permetent que naveguin tant en exteriors com en interiors. Més detalladament, aquesta tesis s’enfronta als seg¨uents reptes: 1) estudi i implementació de la tecnologia Ultra-Wideband (UWB) a la integraci ó estàndard de GNSS/INS; 2) desenvolupament d’una arquitectura d’integraci ó loose/tight híbrida; 3) avaluaci ó de la fusi ó de dades amb diversos sensors (incloent les mesures UWB) tant en navegació terrestre com a` eria, tot utilitzant dades reals per fer les proves; i 4) millorar els resultats obtinguts de la fusi ó per tal de millorar el funcionament del prototip i, per tant, aconseguir una soluci ó per a la navegació molt més precisa. El contingut d’aquesta tesis est à distribu¨ıt en 8 capítols, a més d’una introducci ó i unes conclusions. En primer lloc, s’inclou una introducci ó on es parla del context en el qual està emmarcat el projecte i dels objectius que es volen aconseguir. Seguidament, el Capítol 1 resumeix els procediments i tecnologies desenvolupades durant la ´ ultima dècada per tal de millorar el posicionament en espais privats de GNSS. El Capítol 2 presenta les característiques bàsiques dels principals sensor utilitzats en aquesta tesis. A continuaci´ o, el Capítol 3 exposa els principis del Filtre de Kalman, el qual s’ha fet servir per a la estimació dels paràmetres desitjats. El Capítol 4 descriu les diferents arquitectures d’integraci ó desenvolupades en aquesta tesis i el Capítol 5 fa refer ència a les millores implementades per tal de consolidar l’arquitectura est àndard. Després, el Capítol 6 presenta el prototip utilitzat per a gravar i emmagatzemar el set de dades reals que posteriorment seran emprades per provar el funcionament de la integraci ó GNSS/INS/UWB. El seg¨uent capítol 7 detalla els experiments portats a terme i, posteriorment, es presenten els resultats obtinguts al Capítol 8. Finalment, la ´ ultima part del projecte correspon a les conclusions obtingudes després de realitzar tota la feina presentada pr èviament.In June 2015, the European Commission invested in the development of a new research project, known as TIMON, within the framework of the Horizon 2020 programme. This EU project aims to establish a cooperative ecosystem where people, vehicles and infrastructures are interconnected. TIMON pretends to increase the levels of safety, efficiency and flexibility of land transport systems. Part of this project is carried out in the Centre Tecnològic de Telecomunicacions de Catalunya (CTTC), responsible of developing a positioning platform integrating Inertial Measurement Units (IMUs), which operate with the information acquired by accelerometers and gyroscopes (part of an Inertial Navigation System (INS)), and Global Navigation Satellite System (GNSS), with the goal to provide accurate and reliable navigation information. The goals of this thesis are i) to contribute to the TIMON platform, in order to enhance its navigationcapabilitiesforlandvehiclesand,consequently,achieveabetterperformancein areas where GNSS signals are in part or totally denied, and low-cost INS are not capable to guarantee reliable dead reckoning estimations, and ii) extend its use for UAV indoor/outdoor navigation. In detail, the main objectives of this thesis are: 1) study and integration of UWB technology to the standard GNSS/INS integration architectures; 2) development of a new hybrid loose/tight integration solution; 3) testing the resulting multi-sensor data fusion, including the UWB measurements, for land and air vehicle navigation using real data; and 4) enhance the data fusion results obtained from the measurement campaigns to improve the system performance and, therefore, achieve a better navigation solution. The content of this thesis is distributed in 8 chapters, besides an introduction and conclusions. First, a brief introduction is included to further explain the context in which this project is carried out and the goals to be accomplished. Thereafter, Chapter 1 briefly covers the state-of-the-art methods and technologies developed for improving positioning in GNSS-deniedenvironmentsoverthelastdecade. Chapter2establishesthefundamentals ofthedifferentsensorsusedforthedatafusion(INS,GNSSandUWB).Afterthat,Chapter 3 explains the Kalman Filter-based algorithm that estimates the desired parameters of the system. Subsequently,4describesthedifferentintegrationarchitecturesdevelopedforthis thesis, and 5 covers the enhancements that have been implemented in order to robustify the baseline architecture. After that, Chapter 6 presents the prototype used to capture the real data necessary to test the performance of the GNSS/INS/UWB integration architecture. Once the implementation is described, the real measurement campaigns carried out are detailed in 7 and, the results obtained are presented in Chapter 8. Finally, the last part of this project corresponds to the conclusions obtained after all this work

Selective cytotoxicity of cyclometalated gold(III) complexes on Caco-2 cells is mediated by G2/M cell cycle arrest

New cyclometalated gold(III) complexes with a general structure [Au(C^N)(SR)2] or [Au(C^N)Cl(SR)], where C^N is a biphenyl ligand such as 2-(p-tolyl)pyridinate (tpy), 2-phenylpyridinate (ppy) and 2-benzylpyridinate (bzp) (SR = Spym, S(Me)2pym, 2-thiouracil (2-TU) and thiourea), and also with ethynyl moieties of the type [Au(C^N)(C≡C-Ar)2] (Ar = p-toluene and 2-pyridine) have been synthesized. All of them have been characterized, including X-ray studies of complex [Au(bzp)Cl(Spym)], and these studies have permitted to elucidate that leaving chloride ligand is trans located to CAr atom. After the full characterization, physicochemical properties were measured by evaluating drug-like water solubility and cell permeability (partition coefficient). All these experiments pointed that our complexes present adequate properties to be used as anticancer drugs. Although not all the complexes showed antiproliferative effects on Caco-2 cells, those that did were more cytotoxic than cisplatin; and complex [Au(tpy)Cl(2-TU)] is even more active than auranofin. In addition to this effectiveness, no evidence of cytotoxic effects was observed on considered normal cells (with the exception of [Au(bzp)Cl(2-TU)]. Further action mechanisms studies were performed using these selective complexes, showing cell cycle arrest on the G2/M phase, a proapoptotic behaviour and also the modification of some genes involved in tumorigenesis. Thus, as a result of this investigation, we present a new family of 17 cyclometalated complexes, 6 of them being selective and possible candidates to be used against colon cancer.This work was partially funded by Gobierno de Aragón (Grupo Reconocido A02_20R) and associated EU Regional Developments Funds.Peer reviewe