65,974 research outputs found

    Aspectos cl铆nicos de la COVID-19

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    La transmisi贸n del SARS-CoV-2 generalmente ocurre por gotitas respiratorias de diferente tama帽o. Los s铆ntomas de presentaci贸n suelen incluir fiebre, tos, astenia, mialgia o disnea. La mayor铆a de las personas infectadas son asintom谩ticas o tienen una enfermedad leve, pero una minor铆a desarrolla insuficiencia respiratoria progresiva que requiere hospitalizaci贸n y soporte respiratorio. El tratamiento es fundamentalmente de soporte, sin embargo, en pacientes hospitalizados, algunos agentes antivirales directos (administrados durante los primeros d铆as de la infecci贸n) y el tratamiento inmunomodulador con esteroides y bloqueadores de citocinas (en el periodo de hiperinflamaci贸n), pueden mejorar el pron贸stico. No obstante, se necesitan nuevas mol茅culas antivirales frente a SARS-CoV-2, con buena tolerancia y que se puedan administrar por v铆a oral, para evitar la progresi贸n de la enfermedad, prevenir el contagio en pacientes de riesgo y cortar la cadena de transmisi贸n. La duraci贸n exacta de la inmunidad despu茅s de la infecci贸n natural o la vacunaci贸n a煤n espera un estudio de seguimiento a largo plazo. Despu茅s de una COVID aguda, un n煤mero significativo de pacientes desarrollan diversos s铆ntomas persistentes que, en la mayor铆a de personas, mejoran espont谩neamente a lo largo de las semanas o meses siguientes. La pandemia de COVID-19 ha provocado millones de infecciones en todo el mundo, con morbi-mortalidad significativa, y generado una tensi贸n extrema en los sistemas sanitarios y econ贸micos. La buena noticia es la aparici贸n de vacunas muy eficaces que est谩n ayudando a controlar la enfermedad en pa铆ses desarrollados; de su implementaci贸n masiva durante los pr贸ximos meses, incluyendo a los pa铆ses con menos recursos, va a depender el control adecuado de esta pandemia

    Does international patent collaboration have an effect on entrepreneurship?

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    .Entrepreneurship is one of the main pillars of growth in any economy. Achieving a high rate of entrepreneurship in a region has become the priority objective of governments and firms. However, in many cases, new firm creation is conditioned by relations or collaboration in innovation with agents from other countries. Previous literature has analyzed the mechanisms that foster entrepreneurship. This paper attempts to shed light on the influence of international patent collaboration (IPC) on entrepreneurial activity at country level taking into account the timing of this relationship. An empirical study is proposed to verify whether IPC leads to greater entrepreneurship and to analyze the gestation period between international patenting actions and firm creation. Using the Generalized Method of Moments, the two hypotheses proposed were tested in a data panel of 30 countries for the period 2005鈥2017. Results show the influence of IPC in promoting entrepreneurship in the same year, but especially in the following year. The study offers implications for entrepreneurs and public agents. IPC affects the integration and interaction of international agents in a country, favors the production of new knowledge, and increases positive externalities in a territory. All this facilitates the creation of new companies with a high innovative component.S

    Identification of Hindbrain Neural Substrates for Motor Initiation in the hatchling Xenopus laevis Tadpole

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    Animal survival profoundly depends on the ability to detect stimuli in the environment, process them and respond accordingly. In this respect, motor responses to a sensory stimulation evolved into a variety of coordinated movements, which involve the control of brain centres over spinal locomotor circuits. The hatchling Xenopus tadpole, even in its embryonic stage, is able to detect external sensory information and to swim away if the stimulus is considered noxious. To do so, the tadpole relies on well-known ascending sensory pathway, which carries the sensory information to the brain. When the stimulus is strong enough, descending interneurons are activated, leading to the excitation of spinal CPG neurons, which causes the undulatory movement of swimming. However, the activation of descending interneurons that marks the initiation of motor response appears after a long delay from the sensory stimulation. Furthermore, the long-latency response is variable in time, as observed in the slow-summating excitation measured in descending interneurons. These two features, i.e. long-latency and variability, cannot be explained by the firing time and pattern of the ascending sensory pathway of the Xenopus tadpole. Therefore, a novel neuronal population has been proposed to lie in the hindbrain of the tadpole, and being able to 'hold' the sensory information, thus accounting for the long and variable delay of swim initiation. In this work, the role of the hindbrain in the maintenance of the long and variable response to trunk skin stimulation is investigated in the Xenopustadpole at developmental stage 37/38. A multifaceted approach has been used to unravel the neuronal mechanisms underlying the delayed motor response, including behavioural experiments, electrophysiology analysis of fictive swimming, hindbrain extracellular recordings and imaging experiments. Two novel neuronal populations have been identified in the tadpole's hindbrain, which exhibit activation patterns compatible with the role of delaying the excitation of the spinal locomotor circuit. Future work on cellular properties and synaptic connections of these newly discovered populations might shed light on the mechanism of descending control active at embryonic stage. Identifying supraspinal neuronal populations in an embryonic organism could aid in understanding mechanisms of descending motor control in more complex vertebrates

    Interactive Sonic Environments: Sonic artwork via gameplay experience

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    The purpose of this study is to investigate the use of video-game technology in the design and implementation of interactive sonic centric artworks, the purpose of which is to create and contribute to the discourse and understanding of its effectiveness in electro-acoustic composition highlighting the creative process. Key research questions include: How can the language of electro-acoustic music be placed in a new framework derived from videogame aesthetics and technology? What new creative processes need to be considered when using this medium? Moreover, what aspects of 'play' should be considered when designing the systems? The findings of this study assert that composers and sonic art practitioners need little or no coding knowledge to create exciting applications and the myriad of options available to the composer when using video-game technology is limited only by imagination. Through a cyclic process of planning, building, testing and playing these applications the project revealed advantages and unique sonic opportunities in comparison to other sonic art installations. A portfolio of selected original compositions, both fixed and open are presented by the author to complement this study. The commentary serves to place the work in context with other practitioners in the field and to provide compositional approaches that have been taken

    Balancing the urban stomach: public health, food selling and consumption in London, c. 1558-1640

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    Until recently, public health histories have been predominantly shaped by medical and scientific perspectives, to the neglect of their wider social, economic and political contexts. These medically-minded studies have tended to present broad, sweeping narratives of health policy's explicit successes or failures, often focusing on extraordinary periods of epidemic disease viewed from a national context. This approach is problematic, particularly in studies of public health practice prior to 1800. Before the rise of modern scientific medicine, public health policies were more often influenced by shared social, cultural, economic and religious values which favoured maintaining hierarchy, stability and concern for 'the common good'. These values have frequently been overlooked by modern researchers. This has yielded pessimistic assessments of contemporary sanitation, implying that local authorities did not care about or prioritise the health of populations. Overly medicalised perspectives have further restricted historians' investigation and use of source material, their interpretation of multifaceted and sometimes contested cultural practices such as fasting, and their examination of habitual - and not just extraordinary - health actions. These perspectives have encouraged a focus on reactive - rather than preventative - measures. This thesis contributes to a growing body of research that expands our restrictive understandings of pre-modern public health. It focuses on how public health practices were regulated, monitored and expanded in later Tudor and early Stuart London, with a particular focus on consumption and food-selling. Acknowledging the fundamental public health value of maintaining urban foodways, it investigates how contemporaries sought to manage consumption, food production waste, and vending practices in the early modern City's wards and parishes. It delineates the practical and political distinctions between food and medicine, broadly investigates the activities, reputations of and correlations between London's guild and itinerant food vendors and licensed and irregular medical practitioners, traces the directions in which different kinds of public health policy filtered up or down, and explores how policies were enacted at a national and local level. Finally, it compares and contrasts habitual and extraordinary public health regulations, with a particular focus on how perceptions of and actual food shortages, paired with the omnipresent threat of disease, impacted broader aspects of civic life

    Uso de las histonas circulantes y sus modificaciones post-traduccionales como biomarcadores en sepsis y shock s茅ptico

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    La sepsis es una afecci贸n potencialmente mortal causada por una respuesta anormal del hu茅sped a una infecci贸n, produciendo respuestas fisiol贸gicas alteradas que da帽an los propios tejidos del paciente y pueden provocar disfunci贸n org谩nica e incluso la muerte. Asimismo, algunos pacientes s茅pticos progresan a shock s茅ptico, caracterizado por alteraciones circulatorias, celulares y metab贸licas sustanciales que aumentan el riesgo de mortalidad. A pesar de que la sepsis se caracteriza por un mal funcionamiento del sistema inmunol贸gico, lo que a su vez conduce a una respuesta inmune alterada e inmunosupresi贸n, la alta complejidad de la fisiopatolog铆a de la sepsis requiere una mayor investigaci贸n para comprender las respuestas inmunes que ocurren durante la sepsis. Asimismo, las histonas extracelulares circulantes han ganado relevancia como mediadores citot贸xicos en la sepsis, ya que act煤an como patrones moleculares asociados a da帽o, que inducen estr茅s oxidativo y activan el inflamasoma NLRP3. Estos mecanismos median la activaci贸n de la piroptosis, un mecanismo de muerte celular programada que produce inflamaci贸n mediante la expresi贸n de IL-18, IL-1尾 and IL-1伪. Sin embargo, a pesar de la evidencia de activaci贸n del inflamasoma en las c茅lulas inmunes durante la sepsis, se desconoce si las histonas extracelulares son capaces de activar los inflamasomas endoteliales y sus consecuencias. En este trabajo destacamos el papel previamente desconocido de las histonas extracelulares, mediando la activaci贸n del inflamasoma NLRP3 y la piroptosis en las c茅lulas endoteliales, contribuyendo a la disfunci贸n endotelial y la desregulaci贸n de la respuesta inmune mediada por el endotelio. Asimismo, tambi茅n demostramos c贸mo la acetilaci贸n de histonas disminuye la activaci贸n de la piroptosis. Adem谩s, demostramos que la piroptosis se produce en pacientes con shock s茅ptico y los niveles de histonas circulantes se correlacionan con la expresi贸n de citoquinas proinflamatorias y citoquinas piropt贸ticas, la liberaci贸n de factores de adhesi贸n endotelial y la gravedad de la enfermedad. Proponemos la piroptosis mediada por histonas como un nuevo objetivo para desarrollar intervenciones cl铆nicas. De manera similar, hemos analizado las respuestas inmunorelacionadas que ocurren durante las primeras etapas de la sepsis con el objetivo de proporcionar nuevos datos comparando las cantidades de citoquinas, inmunomoduladores y otros mediadores endoteliales en pacientes cr铆ticamente enfermos no s茅pticos, s茅pticos y de shock s茅ptico. Nuestro enfoque ayudar谩 a caracterizar r谩pidamente las respuestas inmunes alteradas en pacientes s茅pticos y de shock s茅ptico ingresados en la Unidad de Cuidados Intensivos. Finalmente analizamos el papel de la metilaci贸n del ADN en el control del sistema inmune s茅ptico. Nuestros resultados demostraron el papel central de la metilaci贸n del ADN modulando la respuesta molecular en los pacientes de shock s茅ptico y contribuyendo a la inmunosupresi贸n, a trav茅s de la alteraci贸n de los patrones de metilaci贸n de los promotores de IL-10 y TREM-2.Sepsis is a life-threatening condition caused by an abnormal host response to an infection that produce altered physiological responses which damages own tissues of the patient and can result in organ dysfunction and in some cases death. Likewise, a subset of septic patients progresses to septic shock, characterized by substantial circulatory, cellular and metabolic abnormalities, which substantially increase the risk of mortality. Sepsis is characterized by a malfunction of the immune system and it can lead to an altered immune response and immunosuppression. Moreover, the high complexity of the pathophysiology of sepsis requires of further investigation to characterize the immune responses in sepsis and septic shock. Likewise, circulating extracellular histones have gained relevance as cytotoxic mediators in sepsis pathophysiology, since they act as damage-associated molecular patterns, which induce oxidative stress and activate NLRP3 inflammasome. Subsequently, inflammasome mediates pyroptosis activation, a programmed cell death mechanism that produces inflammation through the release of IL-18, IL-1尾 and IL-1伪. However, despite inflammasome activation may occur in immune cells during sepsis, it is unknown if this process also takes place in endothelial cells and particularly whether extracellular histones are capable of activating endothelial inflammasomes and their consequences. In this work we highlight a previously unknown role for extracellular histones, that mediates the activation of NLRP3 inflammasome and pyroptosis in endothelial cells by contributing to endothelial dysfunction and the dysregulation of the immune response mediated by endothelium. Likewise, we demonstrated how histone acetylation decreases pyroptosis activation. Furthermore, we show how pyroptosis occurs in septic shock patients and how circulating histone levels correlate with the expression of pro-inflammatory and pyroptotic cytokines, the release of endothelial adhesion factors and septic shock severity. We propose histone-mediated pyroptosis as a new target to develop clinical interventions. Similarly, we have analyzed the immune-related responses occurring during the early stages of sepsis with the aim of providing new data by comparing the amounts of cytokines, immune modulators and other endothelial mediators in critically-ill non-septic patients, septic and septic shock patients. Our approach will help to rapidly characterize the altered immune responses in septic and septic shock patients admitted in the Intensive Care Unit. Finally, we also analyzed the role of DNA methylation in the control of septic immune system. Our results demonstrated the central role of DNA methylation modulating the molecular response in septic shock patients and contributing to immunosuppression, through the alteration of DNA methylation patterns of IL-10 and TREM2 promoters

    Farmacovigilancia y la relaci贸n con el regente de farmacia

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    Este documento recopila, documenta y resume de una manera muy concreta, la informaci贸n relacionada con la Farmacovigilancia (FV), en el marco del diplomado de profundizaci贸n de dicho tema. A lo largo del curso se abordaron diferentes aspectos de la FV como sus generalidades, los m茅todos y programas de vigilancia, las reacciones adversas, su clasificaci贸n y los tipos de reacciones adversas a medicamentos (RAM), las interacciones entre medicamentos, el quehacer del regente de farmacia, la promoci贸n del uso racional de medicamentos, la efectividad de los mismos y las enfermedades de mayor prevalencia e incidencia en la sociedad.This document compiles, documents and summarizes in a very concrete way, the information related to Pharmacovigilance (VF), around the course. Throughout the course, different aspects of VF were addressed, such as its generalities, surveillance methods and programs, adverse reactions, their classification and the types of adverse drug reactions (ADRs), drug interactions, the regent's work of pharmacy, the promotion of the rational use of medicines, their effectiveness and the diseases with the highest prevalence and incidence in society

    The applied psychology of addictive orientations : studies in a 12-step treatment context.

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    The clinical data for the studies was collected at The PROMIS Recovery Centre, a Minnesota Model treatmentc entre for addictions,w hich encouragesth e membership and use of the 12 step Anonymous Fellowships, and is abstinence based. The area of addiction is contextualised in a review chapter which focuses on research relating to the phenomenon of cross addiction. A study examining the concept of "addictive orientations" in male and female addicts is described, which develops a study conductedb y StephensonM, aggi, Lefever, & Morojele (1995). This presents study found a four factor solution which appeared to be subdivisions of the previously found Hedonism and Nurturance factors. Self orientated nurturance (both food dimensions, shopping and caffeine), Other orientated nurturance (both compulsive helping dimensions and work), Sensation seeking hedonism (Drugs, prescription drugs, nicotine and marginally alcohol), and Power related hedonism (Both relationship dimensions, sex and gambling. This concept of "addictive orientations" is further explored in a non-clinical population, where again a four factor solution was found, very similar to that in the clinical population. This was thought to indicate that in terms of addictive orientation a pattern already exists in this non-clinical population and that consideration should be given to why this is the case. These orientations are examined in terms of gender differences. It is suggested that the differences between genders reflect power-related role relationships between the sexes. In order to further elaborate the significance and meaning behind these orientations, the next two chapters look at the contribution of personality variables and how addictive orientations relate to psychiatric symptomatology. Personality variables were differentially, and to a considerable extent predictably involved with the four factors for both males and females.Conscientiousness as positively associated with "Other orientated Nurturance" and negatively associated with "Sensation seeking hedonism" (particularly for men). Neuroticism had a particularly strong association with the "Self orientated Nurturance" factor in the female population. More than twice the symptomatology variance was explained by the factor scores for females than it was for males. The most important factorial predictors for psychiatric symptomatology were the "Power related hedonism" factor for males, and "Self oriented nurturance" for females. The results are discussed from theoretical and treatment perspectives

    The effect of preservation regime on the physiology and genetic stability of economically important fungi

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    The long-term preservation of fungi has been carried out using several different methods, depending on resources and laboratory. Isolates have been deposited in culture collections for preservation and storage for periods of many years. Despite the widespread use of preservation regimes, little attention has been paid to the poststorage stability of the physiological and genetic characters of strains. The loss of viability of a biological control agent or the failure of an isolate to produce a secondary metabolite pivotal in the production of drugs or food could result in substantial economic loss for the manufacturing organisation. In this investigation the effects of five preservation protocols on fungal characters were assessed: continual sub-culture, lyophilisation, storage in water, storage at -20掳C and cryopreservation in liquid nitrogen The physiology and genetic stability of three species of economically important fungi (Metarhizium anisopliae, Fusarium oxysporum and Serpula lacrymans) were examined by analysis of culture characteristics, secondary metabolite profiling, extracellular enzyme tests and PCR fingerprinting over a two-year testing period. It was found that preservation regime can influence the resultant characters of the test fungi. Radial growth rate and conidial production was changed from the original isolates after preservation and storage. Secondary metabolite profiles from all of the test fungi were susceptible to change by the preservation protocols assessed. Production of some metabolites was lost, whereas others remained stable after preservation and storage. Extracellular enzyme production was also affected in a similar way. For example, some replicates of an isolate of Metarhizium anisopliae lost ~-galactosidase activity after one year of preservation. Genetic stability was also compromised is some isolates. Polymorphisms were detected after PCR fingerprinting with a micro-satellite primer in replicates of two isolates of Metarhizium anisopliae that had been stored for one and two years by cryopreservation and lyophilisation and in two replicates of an isolate of Fusarium oxysporum maintained by continual sub-culture for sixteen weeks. The results indicate that response to preservation and storage is species- and strain-specific. Therefore, there is a need to develop new and existing preservation regimes with emphasis on strain-specific criteria. Scientists should preserve their important isolates by more than one preservation method to protect organisms from the stresses encountered during preservation and storage
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