57,784 research outputs found

    Smartphone-based point-of-care detection systems for infectious diseases

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    Infectious diseases are still among the world’s leading causes of mortality, where disease burden disproportionately impacts the low-income, resource-limited regions. Early detection of infectious disease outbreaks can reduce the ultimate size of the outbreak and the overall morbidity and mortality due to the disease, in which diagnosis plays an important role. As available diagnostic technologies remain expensive, complex, time-consuming, labor-intensive and mainly limited to centralized healthcare facilities or research laboratories, there is an urgent need for low-cost portable platforms that can provide fast, accurate, and ideally multiplex diagnosis of infectious diseases at the point of care. This dissertation reports on the design, fabrication, and demonstration of smartphone-based detection systems for infectious diseases including equine respiratory diseases, coronavirus disease 2019 (COVID-19) and Zika virus disease. Rapid results have been achieved by employing microfluidics-based sample preparation and loop-mediated isothermal amplification (LAMP). The systems have demonstrated high sensitivity and specificity comparable to state-of-the-art laboratory tests. The work reported in this dissertation shows the strong potential of smartphone-based systems for point-of-care diagnosis.LimitedAuthor requested closed access (OA after 2yrs) in Vireo ETD syste

    The thematic and informative agenda on Twitter during the Mandatory Preventive Isolation due to the Coronavirus crisis: politicians, media and opinion leaders in the 2020 pandemic

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    El aislamiento ocasionado por la pandemia del SARS Cov-2 en 2020 llevó a que en la red social Twitter se originaran múltiples discusiones alrededor de las medidas impuestas por el Gobierno colombiano y las consecuencias que tuvieron en la vida de los ciudadanos con el paso de los días. En este trabajo se analizó la correspondencia entre el clima de opinión digital de la red social Twitter, en el que participaron los líderes de opinión, entendidos como los usuarios con más popularidad, y la agenda informativa de los medios con más presencia en ella. Para ello se tomaron las tendencias posicionadas en los primeros lugares durante dos semanas de aislamiento. Se encontró que el Gobierno colombiano fue un protagonista de la mass media, pues a diario produjo y difundió nueva información en el programa Prevención y Acción. Esto permite cuestionar el poder de los medios al imponer una agenda mediática, pues los acontecimientos y las medidas del Gobierno, así como los líderes caracterizados, influenciaron en la repercusión de algunos mensajes con los que los usuarios se sentían más identificados. Al analizar esta información bajo la lupa de la teoría comunicativa de los tres pasos se pudo encontrar que en las redes sociales hay líderes emergentes con potencial para influir en cómo se perciben los acontecimientos por parte de los ciudadanos.The isolation caused by the coronavirus pandemic in 2020 led to multiple discussions on the social network Twitter about the measures imposed by the government and the consequences they had on people’s lives as days went by. In this work, the correspondence between the digital opinion climate of the social network Twitter, in which the opinion leaders, understood as the most popular users, participated and the information agenda of the media with the most presence on it, was analyzed. For this, the trends that occupied the first places for two weeks of isolation were taken into account. It was found that the Colombian government was a protagonist of the mass media, as it produced and spread daily the latest information through the Action and Prevention television show. This makes it possible to question the power of the media by imposing a media agenda since events, government measures and characterized leaders influenced the impact of some messages which users felt more identified with. When analyzing this information under the magnifying glass of the communicative theory of the three steps, it was found that there are emerging leaders in social networks with the potential to influence how citizens perceive events

    Management of head and neck cancer patients during the Covid-19 pandemic

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    The novel coronavirus outbreak point out the need of a paradigm shift in the management of head and neck cancer. A review of literature was performed analyzing the risk of infection in head and neck cancer patients in order to re-organized oncological approach balancing risk of exposition in these immunocompromised patients and risk or tumor progression due to delay in cancer treatment. In this study we propose a new algorithm for the management of head and neck patients at time of diagnosis, therapy and follow u

    C-Glicosil flavonóides como potenciais drogas anticoronavírus com dupla ação

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    The ongoing COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has spread all over the world, causing millions of deaths, and became a major global concern. Although protective vaccines have been developed and administered, efficient antiviral agents for the prevention and treatment of SARS-CoV-2 are not yet available. Moreover, since new and deadly CoVs can emerge at any time with the potential of becoming pandemics, it is crucial the development of therapeutic agents against these potentially deadly CoVs. The scientific research and the medical challenges to save lives revealed the genetic evolution and the biochemistry of SARS-CoV-2 life cycle in comparison with other coronaviruses. The SARS-CoV-2 attacks primarily the respiratory tract, through its binding of Spike glycoprotein to angiotensin converting enzyme 2 (ACE2) of the host cell, initiating the replication and transcription of viral genome by 3CLpro. There have been developed some strategies towards SARS-CoV-2 inhibition, which target the Spike glycoprotein and 3CLpro. In the search for anti-coronaviral drugs, researchers soon turned their heads towards glycosylated flavonoids. Glycosyl flavonoids, widespread in the plant kingdom, have received a lot of attention due to their widely recognized antioxidant, anti-inflammatory, anticarcinogenic, antidiabetic activities, and to their ability to modulate key cellular enzymes function. Recently, glycosyl flavonoids have also shown promising antiviral activity against SARS-CoV-2. Despite O-glycosyl flavonoids are by far the most common in nature, C-glycosyl flavonoids have attracted much recent interest, due to their enhanced stability to chemical and enzymatic hydrolysis. Thus, the first aim of this work was the synthesis of new C-glycosyl flavonoids to evaluate their antiviral activity towards the SARS-CoV-2. The synthesis of C-glycosyl flavonoids was achieved through the cross-coupling Heck reaction between a 3-bromo flavonoid and a modified sugar alkene. Although the synthesis of C-glycosyl flavones was not well-succeeded, it was possible to synthesize C-glycosyl 2-styryl-4H-chromen-4-ones, although, the presence of isomers was observed. The new synthesized compounds were unequivocally characterized by mono- (1H and 13C) and two-dimensional (HSQC, HMBC, NOESY) nuclear magnetic resonance (NMR) spectroscopy techniques. Whenever possible, they were also characterized by mass spectrometry and high-resolution mass spectrometry. Since the new synthesized C-glycosyl 2-styryl-4H-chromen-4-ones were obtained as a mixture of isomers, the evaluation of the antiviral activity could not be performed. Further studies to separate the isomers are needed, as well as the evaluation of the antiviral activity towards the 3CLpro and α-glucosidases. Furthermore, molecular docking studies will be conducted to understand the interactions of the new synthesize C-glycosyl flavonoids with SARS-CoV-2 3CLpro and the α-glucosidases.A pandemia da COVID-19 que decorre atualmente, causada pela Síndrome Respiratória Aguda Grave Coronavírus 2 (SARS-CoV-2), espalhou-se por todo o mundo, causando milhões de mortes, e tornou-se uma preocupação global. Apesar de terem sido desenvolvidas e administradas vacinas, a doença continua ativa e ainda não estão disponíveis terapêuticas antivirais eficazes para a prevenção e o tratamento da SARS-CoV-2. Além disso, uma vez que novos e potencialmente mortais coronavírus (CoVs) podem surgir a qualquer momento com o potencial de se tornarem pandémicos, é crucial o desenvolvimento de agentes terapêuticos contra estes vírus. A pesquisa científica e os desafios médicos para salvar vidas revelaram a evolução genética e a bioquímica do ciclo de vida do SARS-CoV-2 em comparação com outros coronavírus. O SARS-CoV-2 ataca principalmente o trato respiratório, por meio da sua ligação da glicoproteína Spike à enzima conversora de angiotensina 2 (ACE2) da célula hospedeira, iniciando a replicação e transcrição do genoma viral pela 3CLpro. Deste modo, têm vindo a ser desenvolvidas algumas estratégias para a inibição da SARS-CoV-2, que têm como alvo a glicoproteína Spike e a 3CLpro. Na busca por medicamentos anticoronavírus, alguns grupos de investigação têm-se focado no estudo de flavonoides glicosilados. Os glicosil flavonoides, distribuídos abundantemente pelo reino vegetal, têm recebido muita atenção devido às suas atividades antioxidantes, anti-inflamatórias, anti carcinogénicas e antidiabéticas amplamente reconhecidas, e pela sua capacidade de modular a função de enzimas celulares essenciais. Recentemente, os glicosil flavonoides também mostraram atividade antiviral promissora contra o SARS-CoV-2. Apesar de os O-glicosil flavonóides serem os mais comuns na natureza, os C-glicosil flavonoides têm atraído recentemente muito interesse, devido à sua estabilidade à hidrólise química e enzimática. Assim, o primeiro objetivo deste trabalho foi a síntese de novos C-glicosil flavonóides para avaliar sua atividade antiviral contra o SARS-CoV-2. A síntese dos C-glicosil flavonóides foi efetuada através da reação acoplamento de Heck entre um 3-bromo flavonóide e um alceno de açúcar modificado. Embora a síntese de C-glicosil flavonas não tenha sido conseguida, foi possível sintetizar C-glicosil 2-estiril-4H-cromen-4-onas, embora a reação origine uma mistura de isómeros. Os novos compostos obtidos foram caracterizados por técnicas de espectroscopia de ressonância magnética nuclear (RMN) mono- (1H e 13C) e bi-dimensionais (HSQC, HMBC, NOESY). Sempre que possível, foram também caracterizados por espectrometria de massa e espectrometria de massa de alta resolução. Visto que os novos C-glicosil 2-estiril-4H-cromen-4-onas sintetizados possuem isómeros, a avaliação da atividade antiviral não pôde ser efetuada. Mais estudos para separar os isômeros formados são necessários, bem como a avaliação da atividade antiviral frente à 3CLpro e α-glucosidases. Além disso, estudos de docking molecular serão conduzidos para entender as interações dos novos C-glicosil flavonóides sintetizados com a 3CLpro da SARS-CoV-2 e as α-glucosidases.Mestrado em Bioquímic

    Isothermal amplification technologies, alternatives to PCR, for the detection of the SARS-Cov-2 coronavirus and other microbial pathogens

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    RESUMEN : La notificación de una serie de casos de neumonía de etiología desconocida en Wuhan en diciembre de 2019 y la posterior declaración por parte de la Organización Mundial de la Salud el 11 de marzo de 2020, señalaron el comienzo de la actual pandemia por el nuevo coronavirus SARS-CoV-2 en el calendario de la era contemporánea. La nueva pandemia ha supuesto un reto para la comunidad científica y para la asistencia sanitaria a nivel global, ya que el consecuente gran aumento de la demanda asistencial ha evidenciado los fallos del sistema sanitario, pero también la gran capacidad de la ciencia biomédica actual para proporcionar soluciones tecnológicas para hacerla frente a corto plazo y el valor de los profesionales para sobreponerse a la adversidad aportando sus conocimientos sin dosificar el esfuerzo. En un año se ha producido una revolución en la ciencia de las vacunas y del diagnóstico microbiológico. En este trabajo recogemos las últimas aportaciones en este campo, centrándonos en las técnicas moleculares para la detección del SARS-CoV-2, y, en particular, las basadas en la detección de ácidos nucleicos. Entre ellas, algunastécnicas de amplificación isotérmica se proponen como complemento y hasta como alternativa a la PCR en tiempo real, por su sencillez y menor coste. La correcta toma de muestras, el desarrollo de nuevos protocolos y las nuevas técnicas diagnósticas constituyen los pilares fundamentales para mejorar la detección del patógeno, lo que ayudará a controlar la pandemia.ABSTRACT : The notification of a series of pneumonia cases of unknown etiology in Wuhan in December 2019 and the subsequent declaration by the World Health Organization on March 11, 2020, signaled the beginning of the current pandemic due to the new SARS-CoV-2 coronavirus in the contemporary era calendar. The new pandemic has posed a challenge for the scientific community and for health care at a global level, since the consequent large increase in demand for care has shown the failures of the health system, but also the great capacity of current biomedical science to provide technological solutions to face it in the short term and the courage of professionals to overcome adversity by contributing their knowledge without expending effort. In one year there has been a revolution in the science of vaccines and microbiological diagnostics. In this work we collect the latest contributions in this field, focusing on molecular techniques for the detection of SARS-CoV-2, in particular those based on the detection of nucleic acids. Among them, some isothermal amplification techniques are proposed as a complement and even as an alternative to real-time PCR, due to its simplicity and lower cost. Correct sampling, the development of new protocols and new diagnostic techniques constitute the fundamental pillars to improve the detection of the pathogen, which will help to control the pandemic.Grado en Medicin

    Diagnostic profiling of MDSCs in sepsis

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    With 50 million cases and 11 million deaths per year, sepsis is one of the leading causes of death worldwide. Sepsis is caused by a dysregulated host response to an infection, which consists of concurrent inflammatory and immunosuppressive reactions. Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells characterized by their immunosuppressive properties, rising in inflammatory diseases. MDSCs are subdivided into polymorphonuclear MDSCs (PMN-MDSCs) and monocytic MDSCs (M-MDSCs) based on their relationship with mature PMNs and monocytes. It is unknown how their level varies over time in human sepsis. We hypothesized that MDSCs have diagnostic and prognostic potential in sepsis patients. In this thesis, we aimed to illustrate the dynamic profile of MDSCs in critically ill patients in relation to sepsis severity, secondary infections, and mortality. Four study cohorts were used: 1) healthy subjects infused with endotoxin, 2) non-infectious, critically ill patients without antibiotic therapy (PIPOVAP study), 3) hospitalized coronavirus 2019 (COVID-19) patients and, 4) sepsis patients with multi-organ dysfunction syndrome (MODS) (INCLASS study). Serial samples of peripheral blood were used to quantify MDSCs by flow cytometry and FlowSOM to avoid gating biases. M-MDSCs were defined as HLA-DRlow monocytes, and PMN-MDSCs as CD16low granulocytes. Furthermore, we quantified up to 49 cytokines by multiplex bead assay, and analysed the functionality of monocytes and dendritic cells (DCs) in ex vivo stimulated whole blood by intracellular cytokine staining and flow cytometry. Endotoxin infusion in healthy subjects induced a quick, massive, and transient accumulation of MDSCs in peripheral blood. PMN-MDSCs increased 40-fold to reach up to 43% of all granulocytes 6-8 hours after infusion. M-MDSCs increased 10-fold 8 hours after endotoxin infusion comprising more than half of total monocytes. After 24 hours, PMN-MDSCs and M-MDSCs returned to baseline levels. In patients enrolled in the PIPOVAP, COVID-19, and INCLASS studies, the blood concentration of PMN-MDSCs and M-MDSCs were high at study inclusion and correlated to disease severity. In the PIPOVAP study, high levels of M-MDSCs also correlated to the development of secondary gram-negative infections. High MDSCs were associated with mortality in non-infectious critically ill patients (PIPOVAP), but with survival in sepsis patients with MODS (INCLASS). MDSCs correlated with the concentrations of blood cytokines, chemokines, and growth factors in the PIPOVAP and COVID-19 studies. Finally, 3 months after the COVID-19 diagnosis, irrespective of initial disease severity, MDSCs were back to normal levels whilst the production of cytokines by blood cells was still largely affected. Altogether, we report that MDSCs quickly rise during endotoxemia and are associated with sepsis severity. Thus, MDSCs might represent valuable tools to screen vulnerable patients in the intensive care. Additionally, we show for the first time that a high level of MDSCs is associated with improved outcomes in a subset of extremely ill sepsis patients with MODS. Overall, MDSCs may represent sepsis biomarkers and targets of therapy. To pursue clinical development, the quantification method of MDSCs in patients need to be standardized, and the function and plasticity of MDSCs during sepsis should be further explored. -- Avec 50 millions de cas et 11 millions de décès par an, le sepsis est l'une des principales causes de décès dans le monde. Le sepsis est causé par une réponse dérégulée de l'hôte en réponse à une infection, qui consiste en des réactions inflammatoires et immunosuppressives concomitantes. Les cellules suppressives d'origine myéloïde (MDSCs) sont des cellules myéloïdes immatures caractérisées par leurs propriétés immunosuppressives. Les MDSCs sont subdivisées en MDSCs polymorphonucléaires (PMN- MDSCs) et MDSCs monocytaires (M-MDSCs) en fonction de leur relation avec les PMNs et monocytes matures. L’évolution des MDSCs au cours d’un sepsis humain est très peu documentée. Pour combler cette lacune, dans cette thèse nous avons analysé l’expression des MDSCs dans le sang en regard de la sévérité du sepsis et de paramètres immunologiques. Quatre études de cohortes ont été utilisées: 1) des sujets sains perfusés avec de l'endotoxine, un composant de bactéries gram-négatives qui permet de mimer une infection bactérienne (étude endotoxin), 2) des patients non infectieux, hospitalisés aux soins intensifs (SI) (étude PIPOVAP), 3) des patients coronavirus 2019 hospitalisés (étude COVID-19) et 4) des patients sepsis présentant un syndrome de défaillance multiviscérale associé à une mortalité d’environ ~70% (étude INCLASS). Des échantillons sériels de sang périphérique ont été collectés pour quantifier les MDSCs. En outre, nous avons mesuré une cinquantaine de cytokines, chimiokines et facteurs de croissances et analysé la fonctionnalité des globules blancs du sang complet. La perfusion d'endotoxine chez des sujets sains induisait une accumulation rapide, massive (pouvant aller jusqu’à 30-40% de tous les globules blancs) et transitoire de MDSCs. Après 24 heures, les MDSCs étaient revenus à un taux normal. Les MDSCs étaient élevées chez les patients inclus dans les études PIPOVAP, COVID-19 et INCLASS. Cette augmentation corrélait avec la gravité de la maladie et, dans l'étude PIPOVAP, avec le développement d'infections nosocomiales. Des taux élevés de MDSCs étaient associés à la mortalité chez les patients non-infectieux hospitalisés aux SI. Par contre, une accumulation de MDSCs était associée à un devenir favorable chez les patients sepsis ayant développé un syndrome de défaillance multiviscérale. Finalement, chez les patients COVID-19 ré-analysés 3 mois après leur hospitalisation, les MDSCs étaient normales alors que certains dysfonctionnements immunitaires étaient détectés. Ceux-ci qui pourraient être associés au syndrome de « COVID long ». En résumé, nous rapportons que les MDSCs augmentent rapidement et fortement dans le sang d’individus exposés à un composant de bactérie, et qu’elles sont associées à la sévérité du sepsis. Ainsi, les MDSCs ont un potentiel diagnostique et pronostique chez les patients atteints de sepsis. Par ailleurs, les MDSCs pourraient représenter des cibles d’immunothérapie, d’autant plus que des traitements ciblant les MDSCs sont actuellement testées dans le cadre de cancers. -- The immune system protects the human body against infections caused by microorganisms, like viruses and bacteria. White blood cells are one important part of the immune system. White blood cells kill invading organisms as well as warn and activate other white blood cells to increase host defences. However, sometimes the immune system does not respond appropriately to an infection, or it cannot control it. When that happens, white blood cells injure tissues through collateral damage while trying to contain the infection. This can lead to organ failure, which is associated with a high mortality rate. When this happens, it is called sepsis. With 50 million cases and 11 million deaths per year, sepsis is a global health priority. During sepsis, white blood cells can respond too strongly, stop functioning, or even repress the function of other cells. This is called immunosuppression. Immunosuppression can cause long-term effects in recovered sepsis patients, such as the development of new infections and heart diseases. In this thesis, we were interested in a particular type of white blood cells called myeloid-derived suppressor cells (MDSCs). MDSCs restrict the function of other white blood cells. In short, they are immunosuppressive. Healthy people have very few MDSCs, but patients with inflammatory diseases such as cancer, have high levels of MDSCs. How fast MDSCs respond after an infection, and what type of impact these cells have during sepsis are largely unknown. We aimed to give an in-depth view of the dynamics of MDSCs in conditions of inflammation and infection. We set up four studies to address our aim. Blood was collected from individuals at different time intervals to measure MDSCs and other immune parameters. The first study was with healthy volunteers who were injected with bacterial compounds, which trigger white blood cells mimicking bacterial sepsis. We observed that MDSC levels rise strongly 2 hours after infusion and remained high until 8 hours after the injection. MDSCs returned to normal levels after 24 hours. This tells us that MDSCs are very fast responders when the host is triggered by a bacterial compound. In the second study, we tested critically ill patients in the Intensive Care Unit (ICU) without an infection. We noticed that patients with high levels of MDSCs were more likely to become infected and to die. We assume that MDSCs suppressed the function of anti-microbial white blood cells, increasing the risks of infection. In the third study, we looked at COVID-19 patients. COVID-19 patients can develop sepsis, which is one of the reasons why some must be hospitalized. Patients admitted to the ICU had more MDSCs than patients who did not require admission to the ICU. In the fourth study, we analysed severe sepsis patients with multiple organ dysfunctions. Patients with high levels of MDSCs were more likely to survive. Most likely, MDSCs were beneficial in these severe patients because MDSCs were counterbalancing the otherwhite blood cells that were overreacting and damaging. To conclude, this thesis shows 1) how MDSCs are modulated during sepsis, and 2) that MDSCs can be helpful or hurtful depending on the degree of sepsis severity. We propose to use MDSCs as signals of sepsis severity, and possibly as targets of therapy as currently tested in cancer patients. -- Le système immunitaire protège notre organisme contre les infections par les bactéries et les virus. Les globules blancs présents dans le sang sont des éléments vitaux du système immunitaire car ils peuvent tuer les bactéries et les virus. Par ailleurs ils activent d'autres globules blancs, augmentent les défenses de l'hôte, et confèrent la mémoire immunitaire protégeant de réinfections. Il arrive que le système immunitaire ne réponde pas de façon appropriée ou ne peut pas contrôler l’infection. Dans ce cas, les globules blancs peuvent causer des dommages collatéraux aux tissus. Cela peut entraîner une défaillance d’organe, associée à un taux de mortalité élevé. C'est ce qu'on appelle un sepsis. Avec 50 millions de cas et 11 millions de décès par an, le sepsis est une priorité sanitaire mondiale. Lors d’un sepsis, les globules blancs peuvent cesser de fonctionner ou empêcher le fonctionnement d'autres cellules. C'est ce qu'on appelle l'immunosuppression. Elle peut avoir des effets à long terme chez les patients ayant guéris d’un sepsis, comme le développement d’infections et ou de maladies cardiaques. Dans cette thèse, nous nous sommes intéressés aux globules blancs appelés cellules myéloïdes suppressives (MDSCs). Les MDSCs restreignent la fonction des autres globules blancs, elles sont donc immunosuppressives. Les personnes en bonne santé, contrairement à celles atteintes de maladies inflammatoires y compris le cancer, ont très peu de MDSCs dans leur sang. Très peu étant connu quant à l’implication des MDSCs dans le sepsis, notre objectif était de fournir une analyse approfondie de la dynamique des MDSCs dans des conditions d'infection. Nous avons mis en place quatre études pour répondre à notre objectif. Le sang a été prélevé à intervalles réguliers pour mesurer les MDSCs et d'autres paramètres immunologiques. La première étude portait sur des volontaires sains recevant une injection d’un morceau de bactérie simulant un sepsis à bactérie. Les MDSCs augmentaient rapidement, fortement, et transitoirement revenant à un niveau normal 24 heures après l’injection. Dans la deuxième étude, nous avons testé des patients sans infection, admis aux soins intensifs (SI). Nous avons remarqué que les patients avec beaucoup de MDSCs développaient plus d’infections nosocomiales, dont des infections mortelles. Nous pensons que les MDSCs supprimaient la fonction des globules blancs antimicrobiens, augmentant les risques d'infection. Dans la troisième étude, nous avons examiné des patients atteints de COVID-19. Les patients COVID-19 admis aux SI avaient plus de MDSCs que ceux n’ayant pas besoin d'être admis aux SI. Dans la quatrième étude, nous avons analysé des patients atteints de sepsis grave présentant une défaillance de plusieurs organes. Ceux avec beaucoup de MDSCs avaient un pronostique plus favorable. Nous pensons que, dans ce contexte particulièrement sévère (environ 70% des patients décédaient), les MDSCs contrebalançaient la réponse excessive de globules blancs et les dommages collatéraux subséquents. Pour conclure, cette thèse décrit comment les MDSCs sont modulées pendant un sepsis, et que les MDSCs peuvent être utiles ou néfastes selon le degré de sévérité des patients infectés. Les MDSCs pourraient être utilisées comme indicateur de gravité du sepsis, et éventuellement comme cibles de traitements tels que ceux ciblant les MDSCs testés actuellement chez les patients cancéreux. -- Het lichaam wordt door zijn eigen immuunsysteem beschermd tegen indringers zoals virussen en bacteriën. Witte bloedcellen spelen daarbij een belangrijke rol. Ze doden indringers en waarschuwen en activeren andere witte bloedcellen om de afweer te versterken. Soms reageren de witte bloedcellen te sterk of krijgen ze de infectie niet onder controle. In een poging de infectie te bestrijden beschadigen witte bloedcellen dan de weefsels. Deze weefselschade kan leiden tot uitval van organen. De kans op overlijden is hierbij groot. Dit ernstige ziektebeeld wordt sepsis genoemd. Jaarlijks ontwikkelen wereldwijd ongeveer 50 miljoen mensen sepsis waarvan er 11 miljoen overlijden. Na een doorgemaakte sepsis is er kans op langdurige gezondheidsproblemen, zoals bijvoorbeeld nieuwe infecties en hartaandoeningen. Dit komt doordat tijdens sepsis, witte bloedcellen niet alleen te sterk reageren, maar ook stoppen met functioneren en de functie van andere cellen onderdrukken. Dit laatste wordt immunosuppressie genoemd en kan lang aanhouden nadat patiënten van sepsis hersteld zijn. In dit proefschrift onderzochten we een bepaald type witte bloedcel, namelijk “myeloid-derived suppressor cells” (MDSC's). MDSC's onderdrukken de functie van andere witte bloedcellen en werken dus immunosuppressief. In tegenstelling tot gezonde mensen hebben patiënten met ontstekingsziekten zoals kanker of auto-immuunziekten veel MDSC’s. Het is echter nog onbekend hoe snel MDSC’s reageren op een infectie en welke rol zij spelen tijdens sepsis. We hebben vier onderzoeken uitgevoerd om hierin meer inzicht te krijgen. De eerste studie betrof gezonde vrijwilligers die stukjes van bacteriën toegediend kregen. Dit activeert witte bloedcellen en is daarom vergelijkbaar met bacteriële sepsis. We constateerden dat de MDSC-waarden in het bloed 2 uur na toediening sterk stegen en vervolgens verhoogd bleven tot 8 uur na toediening. Na 24 uur keerden MDSC-waarden terug naar normaal. Hieruit kunnen we concluderen dat MDSC's zeer snel reageren wanneer het lichaam wordt geïnfecteerd door een bacterie. De tweede studie betrof ernstig zieke patiënten die initieel geen infectie hadden op de intensive care (IC). In deze groep zagen we dat patiënten met hoge MDSC-waarden een grotere kans hadden om een infectie te ontwikkelen en hierdoor te overlijden. Waarschijnlijk onderdrukten MDSC's de functie van andere infectie-bestrijdende witte bloedcellen, waardoor het infectierisico toenam. De derde studie betrof COVID-19-patiënten. Sommige COVID-19-patiënten ontwikkelen sepsis en moeten worden opgenomen in het ziekenhuis. Wij constateerden dat COVID-19-patiënten die op de IC waren opgenomen, meer MDSC's hadden dan patiënten die op de verpleegafdeling konden blijven. Ten slotte, onderzochten we in vierde studie patiënten met ernstige sepsis bij wie meerdere organen waren uitgevallen. Hier constateerden we dat patiënten met hoge MDSC-waarden een grotere overlevingskans hadden. Hoogstwaarschijnlijk waren MDSC's beschermend bij deze ernstig zieke patiënten omdat MDSC’s de te hevig reagerende witte bloedcellen onder controle brachten. Concluderend toont dit proefschrift hoe MDSC’s zich gedragen tijdens sepsis, en dat MDSC’s therapeutisch of ziekmakend kunnen werken, afhankelijk van de mate van ontsteking in het lichaam. MDSC-waarden kunnen in de toekomst mogelijk gebruikt worden als maat voor ernst van sepsis, en als aangrijpingspunt voor medicatie

    APPLICATION OF CASH FLOW AT RISK METHOD - THE CASE OF MAISTRA D.D. COMPANY

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    Metoda rizičnih novčanih tokova koristan je alat koji može pomoći u analizi i upravljanju rizicima poduzeća. Ovaj će diplomski rad teoretski opisati neke od metoda koje se koriste u integriranom upravljanju rizicima te zatim navedene metode praktično primijeniti u analizi poduzeća Maistra d.d., Rovinj. Uvid u Društvo te njegova vrijednost procijenjena metodom diskontiranih novčanih tokova ukazuje na potencijal za stabilno dugoročno poslovanje, unatoč trenutnim izazovima uzrokovanim pandemijom koronavirusa. Analiza osjetljivosti i scenarija identificirala je ključne rizike koji prijete Društvu te su predložene mjere upravljanja istima. Iako je nužan stalni nadzor rizika, rad zaključuje kako Maistra d.d. efikasno upravlja rizicima na koje može preventivno djelovati.Cash Flow at Risk (CFaR) method is a useful tool that can help in analyzing and managing company risks. This thesis will theoretically describe some of the methods used in enterprise risk management and then apply these methods in the analysis of the company Maistra d.d., Rovinj. Insight into the company and its value estimated using the Discounted Cash Flow (DCF) method indicates the potential for stable long-term operations, despite the current challenges caused by the coronavirus pandemic. Sensitivity and scenario analysis identified key risks that threaten the firm and proposed measures to manage them. Although constant risk monitoring is necessary, the paper concludes that Maistra d.d. efficiently manages preventable risks

    Pregnancy and birth outcomes during the early months of the COVID-19 pandemic

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    ABSTRACT : The new Coronavirus, SARS-CoV-2, is devastating for specific groups of patients, but currently there is not enough information about its effects on pregnant women. The purpose of this study is to identify the impact of SARS-CoV-2 infection on the pregnancy course and the consequences that could cause. We studied a cohort of pregnant ladies who were tested for SARS-CoV-2 infection by RT-PCR, and classified as infected or not infected. The recruitment was made in the HUMV hospital, a third level hospital located in Santander, North of Spain. It started on 23rd March 2020 and ended on 14th October 2020. Data from our cohort was compared with another cohort recruited in 2018 at the same hospital. We found out that gestational hypertension, placental abruptio and home exposure to an infected person, among other variables, could be related with high risk of SARS-CoV-2 infection. In conclusion, we consider pregnant women a high-risk group of patients towards a possible SARS-CoV-2 infection, especially those who present conditions such as gestational hypertension or obesity, moreover we think that SARS CoV-2 infection could increase the possibilities of experimenting an abruptio placentRESUMEN : El nuevo Coronavirus, SARS-CoV-2, es devastador en determinados grupos de pacientes, pero no se ha demostrado aún cómo afecta a las mujeres embarazadas. El propósito de este estudio es identificar el impacto que tiene la infección por SARS-CoV-2 durante el curso del embarazo y las consecuencias que puede acarrear. La metodología del estudio se ha basado en el análisis de una cohorte de embarazadas catalogadas como infectadas o no infectadas mediante test RT-PCR para SARS-CoV-2. La selección de las participantes se realizó en el Hospital Marqués de Valdecilla, en Santander, Norte de España, en el periodo desde el 23 de marzo de 2020 hasta el 14 de octubre del mismo año. Los datos recogidos fueron comparados con los de otra cohorte de embarazadas seleccionada en el mismo hospital en el año 2018. Como resultados, hemos encontrado que la hipertensión gestacional, el desprendimiento prematuro de placenta normo inserta y la ganancia de peso, entre otras variables, podrían aumentar el riesgo de infección por SARS-CoV-2. Como conclusión, creemos que las embarazadas son un grupo de riesgo ante una posible infección por SARS-CoV-2, sobre todo aquellas que presentan adicionalmente hipertensión arterial u obesidad, también creemos que la infección por SARS-CoV-2 podría incrementar las posibilidades de experimentar un abruptio placentae.Grado en Medicin

    Machine Learning Applications in Studying Mental Health Among Immigrants and Racial and Ethnic Minorities: A Systematic Review

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    Background: The use of machine learning (ML) in mental health (MH) research is increasing, especially as new, more complex data types become available to analyze. By systematically examining the published literature, this review aims to uncover potential gaps in the current use of ML to study MH in vulnerable populations of immigrants, refugees, migrants, and racial and ethnic minorities. Methods: In this systematic review, we queried Google Scholar for ML-related terms, MH-related terms, and a population of a focus search term strung together with Boolean operators. Backward reference searching was also conducted. Included peer-reviewed studies reported using a method or application of ML in an MH context and focused on the populations of interest. We did not have date cutoffs. Publications were excluded if they were narrative or did not exclusively focus on a minority population from the respective country. Data including study context, the focus of mental healthcare, sample, data type, type of ML algorithm used, and algorithm performance was extracted from each. Results: Our search strategies resulted in 67,410 listed articles from Google Scholar. Ultimately, 12 were included. All the articles were published within the last 6 years, and half of them studied populations within the US. Most reviewed studies used supervised learning to explain or predict MH outcomes. Some publications used up to 16 models to determine the best predictive power. Almost half of the included publications did not discuss their cross-validation method. Conclusions: The included studies provide proof-of-concept for the potential use of ML algorithms to address MH concerns in these special populations, few as they may be. Our systematic review finds that the clinical application of these models for classifying and predicting MH disorders is still under development
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