98,660 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

    Application of lactic acid bacteria for the biopreservation of meat products: A systematic review

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    .The increasing concern of consumers about food quality and safety and their rejection of chemical additives has promoted the breakthrough of the biopreservation field and the development of studies on the use of beneficial bacteria and their metabolites as potential natural antimicrobials for shelf life extension and enhanced food safety. Control of foodborne pathogens in meat and meat products represents a serious challenge for the food industry which can be addressed through the intelligent use of bio-compounds or biopreservatives. This article aims to systematically review the available knowledge about biological strategies based on the use of lactic acid bacteria to control the proliferation of undesirable microorganisms in different meat products. The outcome of the literature search evidenced the potential of several strains of lactic acid bacteria and their purified or semi-purified antimicrobial metabolites as biopreservatives in meat products for achieving longer shelf life or inhibiting spoilage and pathogenic bacteria, especially when combined with other technologies to achieve a synergistic effect.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

    South Yorkshire low carbon energy supply chains: hydrogen sector summary

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    Bioinformatic characterization of a triacylglycerol lipase produced by Aspergillus flavus isolated from the decaying seed of Cucumeropsis mannii

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    Lipases are enzymes of industrial importance responsible for the hydrolysis of ester bonds of triglycerides. A lipolytic fungus was isolated and subsequently identified based on the ITS sequence analysis as putative Aspergillus flavus with accession number LC424503. The gene coding for extracellular triacylglycerol lipase was isolated from Aspergillus flavus species, sequenced, and characterised using bioinformatics tools. An open reading frame of 420 amino acid sequence was obtained and designated as Aspergillus flavus lipase (AFL) sequence. Alignment of the amino acid sequence with other lipases revealed the presence GHSLG sequence which is the lipase consensus sequence Gly-X1-Ser-X2-Gly indicating that it a classical lipase. A catalytic active site lid domain composed of TYITDTIIDLS amino acids sequence was also revealed. This lid protects the active site, control the catalytic activity and substrate selectivity in lipases. The 3-Dimensional structural model shared 34.08% sequence identity with a lipase from Yarrowia lipolytica covering 272 amino acid residues of the template model. A search of the lipase engineering database using AFL sequence revealed that it belongs to the class GX-lipase, superfamily abH23 and homologous family abH23.02, molecular weight and isoelectric point values of 46.95鈥塊Da and 5.7, respectively. N-glycosylation sites were predicted at residues 164, 236 and 333, with potentials of 0.7250, 0.7037 and 0.7048, respectively. O-glycosylation sites were predicted at residues 355, 358, 360 and 366. A signal sequence of 37 amino acids was revealed at the N-terminal of the polypeptide. This is a short peptide sequence that marks a protein for transport across the cell membrane and indicates that AFL is an extracellular lipase. The findings on the structural and molecular properties of Aspergillus flavus lipase in this work will be crucial in future studies aiming at engineering the enzyme for biotechnology applications

    Structural and Attitudinal Barriers to Bicycle Ownership and Cycle-Based Transport in Gauteng, South Africa

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    Policies that aim to facilitate and promote non-motorised transport (NMT), and in particular cycling, have been developed by many high-income countries facing increasingly congested roads and saturated public transport systems. Such policies are also emerging in many low- and middle-income settings where high rates of urbanisation have led to similar problems with motorised transport. The aim of the present study was to better understand the potential structural and attitudinal barriers to cycle-based transport in one such context: South Africa鈥檚 Gauteng Province, the industrial powerhouse of sub-Saharan Africa that has recently made a firm commitment to NMT. The study focussed on demographic and socioeconomic variation in bicycle and car ownership, and related this to: (1) the reported use of motorised and non-motorised transport (both private and public); and (2) perceived 鈥榩roblems鈥 with cycling. The analyses drew on interviews with key respondents from n鈥=鈥27,490 households conducted in 2013 as part of the third Quality of Life survey undertaken by the Gauteng City Regional Observatory. The survey contained items on three outcomes of interest: household vehicle ownership (bicycles and cars); modes of transport used for the 鈥渢rips鈥 most often made; and respondents鈥 鈥渟ingle biggest problem with鈥 cycling鈥. Respondent- and household-level demographic and socioeconomic determinants of these outcomes were examined using descriptive and multivariable statistical analyses, the latter after adjustment for measured potential confounders identified using a theoretical causal path diagram (in the form of a directed acyclic graph). Of the n鈥=鈥26,469 households providing complete data on all of the variables examined in the present study, only n鈥=鈥8722 (32.9%) owned a car and fewer still (n鈥=鈥2244; 8.4%) owned a bicycle. The ownership of these assets was commonest amongst wealthier, economically active households; and those that owned a car had over five times the odds of also owning a bicycle, even after adjustment for potential confounding (OR 5.17; 95% CI 4.58, 5.85). Moreover, of household respondents who reported making 鈥榯rips鈥 during the preceding month (n鈥=鈥18,209), over two-thirds of those whose households owned a car (70.1%) reported private car-based transport for such trips, while only 3.2% of those owning a bicycle reported cycling. Amongst the specific responses given to the item requesting the 鈥渟ingle biggest problem with鈥 cycling鈥 by far the commonest was 鈥淒on鈥檛 know how to cycle鈥 (32.2%), less than half as many citing 鈥淰ehicle accident risk鈥 (15.9%), and fewer still: 鈥淒estination is too far鈥 (13.9%); 鈥淐rime鈥 (10.3%); 鈥淭oo much effort鈥 (9.2%); or 鈥淟ack of good paths鈥 (4.6%). While the first of these reasons was commonest amongst poorer households, concerns about risk and effort were both most common amongst better educated, economically active and wealthier/better serviced households. In contrast, concerns over (cycle) paths were only common amongst those owning bicycles. The low prevalence of household bicycle ownership, and the disproportionate number of households owning bicycles that also owned cars, might explain the very small proportion of the 鈥榯he trips most often made鈥 that involved cycle-based transport (0.3%), and the preferential use of cars amongst households owning both bicycles and cars. Low levels of bicycle ownership might also explain why so many respondents cited 鈥淒on鈥檛 know how鈥 as the 鈥渟ingle biggest problem with鈥 cycling鈥; although risk and effort were also substantial concerns (presumably for many who did, and some who did not, know how to cycle); the lack of suitable cycle lanes being only primarily a concern for those who actually owned bicycles. Structural and attitudinal barriers to cycle-based transport limit the use of cycle-based transport in Gauteng, not only amongst the vast majority of household respondents who lack the means to cycle (and the means to learn how), but also amongst those dissuaded from learning to cycle, purchasing a bicycle and/or using a bicycle they own by: the risks and effort involved; the lack of suitable cycle paths; and/or because they also own a car and prefer to drive than cycle

    Medicina personalizada en lactantes con c谩ncer: Estudio farmacogen茅tico de polimorfismos relacionados con toxicidad y respuesta a la quimioterapia

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    Introducci贸n La farmacogen茅tica es una herramienta de la 鈥淢edicina personalizada鈥 que contribuye a optimizar los tratamientos antineopl谩sicos, adapt谩ndolos a las caracter铆sticas gen茅ticas particulares de cada individuo, maximizando su eficacia y minimizando su toxicidad. El lactante con c谩ncer es un paciente de particular vulnerabilidad y sus comorbilidades tiene una especial repercusi贸n vital. El estudio farmacogen茅tico en esta poblaci贸n resulta pionero y novedoso en nuestro medio. La identificaci贸n de marcadores predictivos espec铆ficos permitir谩 individualizar m谩s la terap茅utica en esta poblaci贸n tan fr谩gil y mejorar en consecuencia su calidad de vida y su pron贸stico vital. Material y m茅todos Estudio de cohortes ambispectivo de pacientes oncol贸gicos entre 1 y 18 meses de edad, receptores de quimioterapia en el Hospital La Fe de Valencia, en el periodo comprendido entre enero 2007 y agosto 2019. La parte retrospectiva comprende hasta diciembre 2015, el estudio prospectivo desde enero 2016 hasta agosto 2019. En primer lugar, se realiza un an谩lisis descriptivo de variables epidemiol贸gicas, cl铆nico/biol贸gicas, terap茅uticas y pron贸sticas de 72 pacientes con dichas caracter铆sticas. Se describe la toxicidad derivada de sus 578 ciclos de quimioterapia (37 variables cl铆nicas), el tiempo de seguimiento y su supervivencia (meses). En segundo lugar, se realiza un estudio anal铆tico cuyo objetivo es correlacionar los polimorfismos gen茅ticos relacionados con la quimioterapia de 64 de los pacientes, la toxicidad grave secundaria al tratamiento (鈮 grado 3 seg煤n CTAE 4.0) y su supervivencia. El genotipado se realiza en el Centro Nacional de Genotipado (CEGEN) mediante la tecnolog铆a MassArray (AgenaBioscience), previa configuraci贸n de un panel farmacogen茅tico pedi谩trico en base a las evidencias recogidas en la base de datos PharmGKB, fichas t茅cnicas de los medicamentos y consorcios internacionales expertos. El an谩lisis estad铆stico descriptivo se realiza con los programas Excel 2016 y R: las variables cualitativas con el recuento num茅rico (porcentaje) y las variables cuantitativas como mediana +/- rango intercuart铆lico ante ausencia de normalidad en la distribuci贸n de los datos (p <0,05, prueba de Kolmogorov-Smirnov). En el an谩lisis de supervivencia se utiliza el estimador Kaplan-Meier. El an谩lisis estad铆stico anal铆tico de correlaci贸n entre polimorfismos y toxicidad se realiza mediante regresi贸n log铆stica penalizada por Elastic Net empleando R. El an谩lisis estad铆stico anal铆tico de correlaci贸n entre polimorfismos y reca铆da/muerte se realiza mediante regresi贸n de Cox penalizada por Elastic Net. Resultados Las variables epidemiol贸gicas, cl铆nico/biol贸gicas y terap茅uticas de los pacientes de la muestra son consecuentes con las descritas en la literatura del lactante con c谩ncer. Las neoplasias con mayor impacto negativo en la supervivencia son la leucemia mielobl谩stica aguda y los tumores del sistema nervioso central. La toxicidad m谩s prevalente es hematol贸gica, digestiva e infecciosa. Existe correlaci贸n entre la toxicidad grave secundaria a los quimioter谩picos en forma de anemia, neutropenia y/o trombopenia y 46 polimorfismos gen茅ticos diferentes. As铆 mismo se encuentra asociaci贸n estad铆sticamente significativa entre la supervivencia global y la supervivencia libre de enfermedad y ciertos polimorfismos gen茅ticos (26 y 13 respectivamente). Los polimorfismos obtenidos pertenecen a genes encargados del transporte (6 genes) y metabolismo (17 genes) de los f谩rmacos, de la reparaci贸n del material gen茅tico y la supresi贸n tumoral (5 genes) y de otras funciones biol贸gicas (4 genes). Conclusi贸n Los resultados del presente estudio muestran correlaci贸n estad铆stica entre 46 polimorfismos de genes implicados en la cin茅tica farmacol贸gica y la reparaci贸n del material gen茅tico y la variabilidad en la toxicidad quimioter谩pica y supervivencia de pacientes lactantes con c谩ncer. En definitiva, aportaciones de la farmacogen茅tica que pueden contribuir a la optimizaci贸n del tratamiento antineopl谩sico en esta poblaci贸n particular y a la predicci贸n de sus riesgos, de especial impacto en los supervivientes del c谩ncer infantil

    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

    Rainfall Prediction: A Comparative Analysis of Modern Machine Learning Algorithms for Time-Series Forecasting

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    Rainfall forecasting has gained utmost research relevance in recent times due to its complexities and persistent applications such as flood forecasting and monitoring of pollutant concentration levels, among others. Existing models use complex statistical models that are often too costly, both computationally and budgetary, or are not applied to downstream applications. Therefore, approaches that use Machine Learning algorithms in conjunction with time-series data are being explored as an alternative to overcome these drawbacks. To this end, this study presents a comparative analysis using simplified rainfall estimation models based on conventional Machine Learning algorithms and Deep Learning architectures that are efficient for these downstream applications. Models based on LSTM, Stacked-LSTM, Bidirectional-LSTM Networks, XGBoost, and an ensemble of Gradient Boosting Regressor, Linear Support Vector Regression, and an Extra-trees Regressor were compared in the task of forecasting hourly rainfall volumes using time-series data. Climate data from 2000 to 2020 from five major cities in the United Kingdom were used. The evaluation metrics of Loss, Root Mean Squared Error, Mean Absolute Error, and Root Mean Squared Logarithmic Error were used to evaluate the models' performance. Results show that a Bidirectional-LSTM Network can be used as a rainfall forecast model with comparable performance to Stacked-LSTM Networks. Among all the models tested, the Stacked-LSTM Network with two hidden layers and the Bidirectional-LSTM Network performed best. This suggests that models based on LSTM-Networks with fewer hidden layers perform better for this approach; denoting its ability to be applied as an approach for budget-wise rainfall forecast applications
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