131,235 research outputs found

    Comparison of physical fitness between healthy and mild‚Äźto‚Äźmoderate asthmatic children with exercise symptoms: A cross‚Äźsectional study

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    .Objective Asthma is a chronic disease that may affect physical fitness, although its primary effects on exercise capacity, muscle strength, functionality and lifestyle, in children and adolescents, are still poorly understood. This study aimed to evaluate the differences in cardiorespiratory fitness, muscle strength, lifestyle, lung function, and functionality between asthmatics with exercise symptoms and healthy children. In addition, we have analyzed the association between clinical history and the presence of asthma. Study Design Cross-sectional study including 71 patients with a diagnosis of asthma and 71 healthy children and adolescents (7‚Äď17 years of age). Anthropometric data, clinical history, disease control, lifestyle (KIDMED and physical activity questionnaires), lung function (spirometry), exercise-induced bronchoconstriction test, aerobic fitness (cardiopulmonary exercise test), muscle strength and functionality (timed up and go; timed up and down stairs) were evaluated. Results Seventy-one patients with asthma (mean age 11.5‚ÄȬĪ‚ÄČ2.7) and 71 healthy subjects (mean age 10.7‚ÄȬĪ‚ÄČ2.5) were included. All asthmatic children had mild to moderate and stable asthma. EIB occurred in 56.3% of asthmatic children. Lung function was significantly (p‚ÄČ<‚ÄČ.05) lower in the asthmatic group when compared to healthy peers, as well as the cardiorespiratory fitness, muscle strength, lifestyle and functionality. Moreover, asthmatic children were more likely to have atopic dermatitis, allergic reactions, food allergies, and a family history of asthma when compared to healthy children. Conclusions Children with mild-to-moderate asthma presenting exercise symptoms show a reduction in cardiorespiratory fitness, muscle strength, lung function, functionality, and lifestyle when compared to healthy peers. The study provides data for pediatricians to support exercise practice aiming to improve prognosis and quality of life in asthmatic children.S

    Aspectos clínicos de la COVID-19

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

    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

    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‚ÄČKDa 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

    Medicina personalizada en lactantes con cáncer: Estudio farmacogenético de polimorfismos relacionados con toxicidad y respuesta a la quimioterapia

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

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

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    La sepsis es una afecci√≥n potencialmente mortal causada por una respuesta anormal del hu√©sped a una infecci√≥n, produciendo respuestas fisiol√≥gicas alteradas que da√Īan los propios tejidos del paciente y pueden provocar disfunci√≥n org√°nica e incluso la muerte. Asimismo, algunos pacientes s√©pticos progresan a shock s√©ptico, caracterizado por alteraciones circulatorias, celulares y metab√≥licas sustanciales que aumentan el riesgo de mortalidad. A pesar de que la sepsis se caracteriza por un mal funcionamiento del sistema inmunol√≥gico, lo que a su vez conduce a una respuesta inmune alterada e inmunosupresi√≥n, la alta complejidad de la fisiopatolog√≠a de la sepsis requiere una mayor investigaci√≥n para comprender las respuestas inmunes que ocurren durante la sepsis. Asimismo, las histonas extracelulares circulantes han ganado relevancia como mediadores citot√≥xicos en la sepsis, ya que act√ļan como patrones moleculares asociados a da√Īo, que inducen estr√©s oxidativo y activan el inflamasoma NLRP3. Estos mecanismos median la activaci√≥n de la piroptosis, un mecanismo de muerte celular programada que produce inflamaci√≥n mediante la expresi√≥n de IL-18, IL-1ő≤ and IL-1őĪ. Sin embargo, a pesar de la evidencia de activaci√≥n del inflamasoma en las c√©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√≥n del inflamasoma NLRP3 y la piroptosis en las c√©lulas endoteliales, contribuyendo a la disfunci√≥n endotelial y la desregulaci√≥n de la respuesta inmune mediada por el endotelio. Asimismo, tambi√©n demostramos c√≥mo la acetilaci√≥n de histonas disminuye la activaci√≥n de la piroptosis. Adem√°s, demostramos que la piroptosis se produce en pacientes con shock s√©ptico y los niveles de histonas circulantes se correlacionan con la expresi√≥n de citoquinas proinflamatorias y citoquinas piropt√≥ticas, la liberaci√≥n de factores de adhesi√≥n endotelial y la gravedad de la enfermedad. Proponemos la piroptosis mediada por histonas como un nuevo objetivo para desarrollar intervenciones cl√≠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√≠ticamente enfermos no s√©pticos, s√©pticos y de shock s√©ptico. Nuestro enfoque ayudar√° a caracterizar r√°pidamente las respuestas inmunes alteradas en pacientes s√©pticos y de shock s√©ptico ingresados en la Unidad de Cuidados Intensivos. Finalmente analizamos el papel de la metilaci√≥n del ADN en el control del sistema inmune s√©ptico. Nuestros resultados demostraron el papel central de la metilaci√≥n del ADN modulando la respuesta molecular en los pacientes de shock s√©ptico y contribuyendo a la inmunosupresi√≥n, a trav√©s de la alteraci√≥n de los patrones de metilaci√≥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-1ő≤ and IL-1őĪ. 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

    Making School Streets Healthier: Learning from temporary and emergency closures

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    The Healthy Streets Everyday (HSE) programme began in 2019 to promote active, safe, and sustainable travel in London. In line with the Mayor‚Äôs Transport Strategy, this programme emphasises the Healthy Streets approach, which recognises that promoting health on London‚Äôs streets requires supporting the diverse ways streets are used, including active travel, by making them safer and more accessible to all. School Streets ‚Äď the temporary closure of streets in front of schools to motor vehicle traffic at the beginning and end of the school day ‚Äď have recently emerged as a key intervention in this approach. The connection between streets and broader public health is perhaps nowhere starker than at the school gates. With over 20% of peak- time traffic associated with the school run, traffic and congestion are concentrated at the cramped residential streets that often serve London‚Äôs schools. This puts children at greater risk from road danger and poor air quality. These challenging conditions have been exacerbated by Covid-19; specifically, the need for physical distancing and concern about the effects of a car-based recovery. In response, there has been significant growth in School Streets since the beginning of 2020, with more than 400 currently in place across London. The HSE programme played an important part in providing support to 16 of London‚Äôs boroughs as they implemented their School Streets programmes, often for the first time. As a crucial part of Transport for London‚Äôs Covid-19 Streetspace scheme many of these recent School Streets have been implemented as temporary or emergency interventions, employing light-touch and low-cost approaches such as mobile traffic camera enforcement or temporary barriers. This report sets out several key findings from the close observation of two School Streets: 1. Significant reductions in motor vehicle traffic both during the closure time and over the whole day. 2. Minimal change in pedestrian numbers and use of space, with some evidence of increased cycling. 3. Improvements in several Healthy Streets indicators. Following from these findings and considering more comprehensive academic research, this report also outlines four recommendations for designers and policymakers to consider when making School Streets more permanent or implementing new schemes: 1.Taking a whole school and whole route approach 2.Reducing traffic effectively through enforcement and exemptions 3.Completing a scheme by changing the public realm 4.Designing for and responding to scheme issues through in-depth monitoring and evaluatio

    The second wave of COVID-19 and beyond: Rural healthcare

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    There are increasing signs that SARS-CoV-2 has started to spread to rural areas in India. It impacts people’s health, lives, and public health infrastructure that is already strained from a lack of resources. The emergence of the COVID-19 pandemic in rural India is a worrying trend; 50% of reported cases since the beginning of May 2021 are from rural districts. Long-standing systemic, functional, and health inequities have put people in rural communities at increased risk of contracting COVID-19 and suffering from the lack of essential healthcare services. Health disparities between rural and urban areas exist not only in terms of risk factors, such as poor diet and vaccine hesitancy, but also in terms of healthcare infrastructure, manpower, and testing facilities. We suggest some long-term and short-term measures to efficiently develop strategies to contain and control the pandemic in rural areas. Short-term measures include implementing health communication tailored in culturally sensitive ways, increasing vaccination by the usual immunisation pattern, increasing the number of testing facilities, and ensuring food security through the public distribution system (PDS). Long-term suggestions include strengthening the primary healthcare system, increasing funding in the health sector to 2.5% of the gross domestic product (GDP), introducing mid-level care providers, improving skills and training of ASHAs along with adequate financial incentives, and ensuring participation of multiple stakeholders in community health schemes
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