28 research outputs found

    Hemodynamic Effects of Anthrax Toxins in the Rabbit Model and the Cardiac Pathology Induced by Lethal Toxin

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    Anthrax lethal toxin (LeTx) and edema toxin (EdTx) have been shown to alter hemodynamics in the rodent model, while LeTx primarily is reported to induce extensive tissue pathology. However, the rodent model has limitations when used for comparison to higher organisms such as humans. The rabbit model, on the other hand, has gained recognition as a useful model for studying anthrax infection and its pathophysiological effects. In this study, we assessed the hemodynamic effects of lethal toxin (LeTx) and edema toxin (EdTx) in the rabbit model using physiologically relevant amounts of the toxins. Moreover, we further examine the pathological effects of LeTx on cardiac tissue. We intravenously injected Dutch-belted rabbits with either low-dose and high-dose recombinant LeTx or a single dose of EdTx. The animals’ heart rate and mean arterial pressure were continuously monitored via telemetry until either 48 or 72 h post-challenge. Additional animals challenged with LeTx were used for cardiac troponin I (cTnI) quantitation, cardiac histopathology, and echocardiography. LeTx depressed heart rate at the lower dose and mean arterial pressure (MAP) at the higher dose. EdTx, on the other hand, temporarily intensified heart rate while lowering MAP. Both doses of LeTx caused cardiac pathology with the higher dose having a more profound effect. Lastly, left-ventricular dilation due to LeTx was not apparent at the given time-points. Our study demonstrates the hemodynamic effects of anthrax toxins, as well as the pathological effects of LeTx on the heart in the rabbit model, and it provides further evidence for the toxins’ direct impact on the heart

    The development of the program SQP 2.0 for the prediction of the quality of survey questions

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    Working paper number 24 of the series of the Research and Expertise Centre for Survey Methodology (RECSM)

    Telemetric left ventricular monitoring using wireless telemetry in the rabbit model

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    Abstract Background Heart failure is a critical condition that affects many people and often results from left ventricular dysfunction. Numerous studies investigating this condition have been performed using various model systems. To do so, investigators must be able to accurately measure myocardial performance in order to determine the degree of left ventricular function. In this model development study, we employ a wireless telemetry system purchased from Data Sciences International to continuously assess left ventricular function in the rabbit model. Findings We surgically implanted pressure-sensitive catheters fitted to wireless radio-transmitters into the left ventricle of Dutch-belted rabbits. Following recovery of the animals, we continuously recorded indices of cardiac contractility and ventricular relaxation at baseline for a given time period. The telemetry system allowed us to continuously record baseline left ventricular parameters for the entire recording period. During this time, the animals were unrestrained and fully conscious. The values we recorded are similar to those obtained using other reported methods. Conclusions The wireless telemetry system can continuously measure left ventricular pressure, cardiac contractility, and cardiac relaxation in the rabbit model. These results, which were obtained just as baseline levels, substantiate the need for further validation in this model system of left ventricular assessment.</p

    Efecto de una intervención en línea de cambio en el estilo de vida sobre el puntaje zIMC de escolares mexicanos: protocolo de ensayo controlado aleatorizado piloto cegado a evaluadores durante la pandemia por COVID-19

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    ABSTRACT Introduction: School closures due to the COVID-19 pandemic represent a risk factor for the development of childhood obesity, due to the increase in unhealthy behaviors. Online lifestyle interventions in schoolchildren could help to mitigate this problem. However, to our knowledge, no randomized controlled trials have been conducted to prevent obesity in schoolchildren during COVID-19. The aim of this study is to evaluate the effect of a 4-month online lifestyle intervention on the BMI Z-score of Mexican schoolchildren during the COVID-19 pandemic in an intervention group compared to a control group. Material and Methods: This is a protocol for an outcome assessor-blinded pilot randomized controlled trial. Schoolchildren from a public elementary school in Hermosillo, Sonora, Mexico will be invited to participate. Participants will be randomized to an intervention group (online lifestyle intervention) or a control group. The intervention will include online sessions of nutrition education and physical activity (60 minutes per session, 30 minutes for nutrition education and 30 minutes for physical activity) and nutrition information for parents. The control group will receive a digital brochure with nutrition recommendations at the beginning of the study and access to the program materials at the end of the study. The measurements will be performed at baseline and at 4 months. The primary outcome will be the BMI Z- score. Secondary outcomes will be waist circumference, body fat percentage, nutrition knowledge, lifestyle parameters, participation, retention and acceptance of the intervention. The changes on the outcomes will be analyzed using an intention to treat analysis. The protocol was approved by the Research Ethics Committee of the University of Sonora Nursing Department and registered in Clinical Trials. Conclusion: To our knowledge, the study will provide the first evidence of the evaluation of online interventions for the prevention of obesity in schoolchildren derived from a randomized controlled trial, which could be useful in the fight against childhood obesity.RESUMEN Introducción:  El cierre de escuelas por la pandemia de COVID-19, representa un factor de riesgo para el desarrollo de obesidad en los niños, debido al aumento de conductas no saludables. Las intervenciones de cambio de estilo de vida en línea en escolares podrían ayudar a mitigar este problema. Sin embargo, en nuestro conocimiento no se han realizado ensayos controlados aleatorizados para prevenir obesidad en escolares durante COVID-19. El objetivo del presente estudio es evaluar el efecto de una intervención en línea de cambio de estilo de vida sobre el puntaje Z de IMC de escolares mexicanos a 4 meses durante la pandemia por COVID-19 en un grupo intervención en comparación a un control. Material y Métodos: Protocolo de un ensayo controlado aleatorizado piloto cegado a los evaluadores. Se invitará a participar a escolares de una primaria pública de Hermosillo, Sonora, México. Los participantes serán aleatorizados a un grupo de intervención o a un grupo control. La intervención incluirá 3 sesiones semanales en línea de educación nutricional y actividad física (60 minutos por sesión, 30 minutos de educación nutricional y 30 minutos para la actividad física) e información para padres de familia. El grupo control recibirá un folleto digital con recomendaciones de una dieta saludable al inicio del estudio y acceso a los materiales del programa al finalizar. Las mediciones del estudio se realizarán al inicio y a los 4 meses. La variable primaria será el puntaje Z de IMC. Las variables secundarias serán circunferencia de cintura, porcentaje de grasa, conocimientos en nutrición, parámetros de estilo de vida, retención, aceptación y participación en la intervención.  Los cambios de las variables se analizarán mediante pruebas de comparación de medias por intención de tratamiento. El protocolo fue aprobado por el Comité de Ética en Investigación del Departamento de Enfermería de la Universidad de Sonora y registrado en la plataforma Clinical Trials. Conclusión: En nuestro conocimiento, el estudio aportará la primera evidencia de la evaluación de intervenciones en línea para la prevención de obesidad en escolares derivada de un ensayo controlado aleatorizado, lo cual podría ser útil en el combate de la obesidad infantil

    Efecto de una intervención en línea de cambio en el estilo de vida sobre el puntaje zIMC de escolares mexicanos: protocolo de ensayo controlado aleatorizado piloto cegado a evaluadores durante la pandemia por COVID-19

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    Introduction: School closures due to the COVID-19 pandemic represent a risk factor for the development of childhood obesity, due to the increase in unhealthy behaviors. Online lifestyle interventions in schoolchildren could help to mitigate this problem. However, to our knowledge, no randomized controlled trials have been conducted to prevent obesity in schoolchildren during COVID-19. The aim of this study is to evaluate the effect of a 4-month online lifestyle intervention on the BMI Z-score of Mexican schoolchildren during the COVID-19 pandemic in an intervention group compared to a control group. Material and Methods: This is a protocol for an outcome assessor-blinded pilot randomized controlled trial. Schoolchildren from a public elementary school in Hermosillo, Sonora, Mexico will be invited to participate. Participants will be randomized to an intervention group (online lifestyle intervention) or a control group. The intervention will include online sessions of nutrition education and physical activity (60 minutes per session, 30 minutes for nutrition education and 30 minutes for physical activity) and nutrition information for parents. The control group will receive a digital brochure with nutrition recommendations at the beginning of the study and access to the program materials at the end of the study. The measurements will be performed at baseline and at 4 months. The primary outcome will be the BMI Z- score. Secondary outcomes will be waist circumference, body fat percentage, nutrition knowledge, lifestyle parameters, participation, retention and acceptance of the intervention. The changes on the outcomes will be analyzed using an intention to treat analysis. The protocol was approved by the Research Ethics Committee of the University of Sonora Nursing Department and registered in Clinical Trials. Conclusion: To our knowledge, the study will provide the first evidence of the evaluation of online interventions for the prevention of obesity in schoolchildren derived from a randomized controlled trial, which could be useful in the fight against childhood obesity.Introducción: El cierre de escuelas por la pandemia de COVID-19, representa un factor de riesgo para el desarrollo de obesidad en los niños, debido al aumento de conductas no saludables. Las intervenciones de cambio de estilo de vida en línea en escolares podrían ayudar a mitigar este problema. Sin embargo, en nuestro conocimiento no se han realizado ensayos controlados aleatorizados para prevenir obesidad en escolares durante COVID-19. El objetivo del presente estudio es evaluar el efecto de una intervención en línea de cambio de estilo de vida sobre el puntaje Z de IMC de escolares mexicanos a 4 meses durante la pandemia por COVID-19 en un grupo intervención en comparación a un control. Material y Métodos: Protocolo de un ensayo controlado aleatorizado piloto cegado a los evaluadores. Se invitará a participar a escolares de una primaria pública de Hermosillo, Sonora, México. Los participantes serán aleatorizados a un grupo de intervención o a un grupo control. La intervención incluirá 3 sesiones semanales en línea de educación nutricional y actividad física (60 minutos por sesión, 30 minutos de educación nutricional y 30 minutos para la actividad física) e información para padres de familia. El grupo control recibirá un folleto digital con recomendaciones de una dieta saludable al inicio del estudio y acceso a los materiales del programa al finalizar. Las mediciones del estudio se realizarán al inicio y a los 4 meses. La variable primaria será el puntaje Z de IMC. Las variables secundarias serán circunferencia de cintura, porcentaje de grasa, conocimientos en nutrición, parámetros de estilo de vida, retención, aceptación y participación en la intervención. Los cambios de las variables se analizarán mediante pruebas de comparación de medias por intención de tratamiento. El protocolo fue aprobado por el Comité de Ética en Investigación del Departamento de Enfermería de la Universidad de Sonora y registrado en la plataforma Clinical Trials. Conclusión: En nuestro conocimiento, el estudio aportará la primera evidencia de la evaluación de intervenciones en línea para la prevención de obesidad en escolares derivada de un ensayo controlado aleatorizado, lo cual podría ser útil en el combate de la obesidad infantil

    Affinity-matured homotypic interactions induce spectrum of PfCSP structures that influence protection from malaria infection

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    Abstract The generation of high-quality antibody responses to Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP), the primary surface antigen of Pf sporozoites, is paramount to the development of an effective malaria vaccine. Here we present an in-depth structural and functional analysis of a panel of potent antibodies encoded by the immunoglobulin heavy chain variable (IGHV) gene IGHV3-33, which is among the most prevalent and potent antibody families induced in the anti-PfCSP immune response and targets the Asn-Ala-Asn-Pro (NANP) repeat region. Cryo-electron microscopy (cryo-EM) reveals a remarkable spectrum of helical antibody-PfCSP structures stabilized by homotypic interactions between tightly packed fragments antigen binding (Fabs), many of which correlate with somatic hypermutation. We demonstrate a key role of these mutated homotypic contacts for high avidity binding to PfCSP and in protection from Pf malaria infection. Together, these data emphasize the importance of anti-homotypic affinity maturation in the frequent selection of IGHV3–33 antibodies and highlight key features underlying the potent protection of this antibody family
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