Transcription of toll-like receptors 2, 3, 4 and 9, FoxP3 and Th17 cytokines in a susceptible experimental model of canine Leishmania infantum infection

Canine leishmaniosis (CanL) due to Leishmania infantum is a chronic zoonotic systemic disease resulting from complex interactions between protozoa and the canine immune system. Toll-like receptors (TLRs) are essential components of the innate immune system and facilitate the early detection of many infections. However, the role of TLRs in CanL remains unknown and information describing TLR transcription during infection is extremely scarce. The aim of this research project was to investigate the impact of L. infantum infection on canine TLR transcription using a susceptible model. The objectives of this study were to evaluate transcription of TLRs 2, 3, 4 and 9 by means of quantitative reverse transcription polymerase chain reaction (qRT-PCR) in skin, spleen, lymph node and liver in the presence or absence of experimental L. infantum infection in Beagle dogs. These findings were compared with clinical and serological data, parasite densities in infected tissues and transcription of IL-17, IL-22 and FoxP3 in different tissues in non-infected dogs (n = 10), and at six months (n = 24) and 15 months (n = 7) post infection. Results revealed significant down regulation of transcription with disease progression in lymph node samples for TLR3, TLR4, TLR9, IL-17, IL-22 and FoxP3. In spleen samples, significant down regulation of transcription was seen in TLR4 and IL-22 when both infected groups were compared with controls. In liver samples, down regulation of transcription was evident with disease progression for IL-22. In the skin, upregulation was seen only for TLR9 and FoxP3 in the early stages of infection. Subtle changes or down regulation in TLR transcription, Th17 cytokines and FoxP3 are indicative of the silent establishment of infection that Leishmania is renowned for. These observations provide new insights about TLR transcription, Th17 cytokines and Foxp3 in the liver, spleen, lymph node and skin in CanL and highlight possible markers of disease susceptibility in this model

Correlation between Permeability and Porosity for Pervious Concrete

The aim of this study was to propose a correlation for the hydraulic parameters of pervious concrete (PC). Thus, three aggregates from civil construction waste and one basalt aggregate (reference) were used to produce PC. The ratio c/a (cement: aggregate) 1:3.26 and a w/c ratio of 0.34 were used in all mixtures. Compressive and flexure tensile strength tests were performed to mechanically characterize the mixtures produced, whereas porosity and constant head permeability tests were also carried out to assess the material hydraulic properties. Firstly, the experimental results were compared with the requirements established in international guidelines (ACI 522R-10, NBR 16416 (2015) and VTT-R-080225-13). The results complied with the guidelines indicating it is feasible to produce pervious concretes with the sustainable aggregates used in the study in low structural applications such as walkways. On the other hand, a correlation between permeability and porosity was proposed based on Darcy’s and Bernoulli’s laws. The proposed equation, obtained by means of a non-linear regression, is an exponential equation that characterizes the hydraulic efficiency of the internal channels of the material considering the pores interconnection. The correlation between porosity and permeability was finally validated using results from the literature showing the same trend found in laboratory, and therefore it was demonstrated that the proposed correlation in an efficient tool to predict the hydraulic efficiency of pervious concreteEl objetivo de este estudio fue proponer una correlación para los parámetros hidráulicos del concreto permeable (CoPe). Para esto, se utilizaron 3 agregados de residuos de construcción civil y 1 agregado de basalto como referencia para producir CoPe. La relación 1: 3.26(cemento: agregado) se trabajó en todas las mezclas, una relación a/c de 0.34. Se realizaron pruebas de resistencia a la compresión y resistencia a la flexión para caracterizar mecánicamente el concreto producido y verificar el cumplimiento con los estándares ACI 522R-10, NBR 16416 (2015) y VTT-R-080225-13. También se llevaron a cabo pruebas de porosidad y permeabilidad a carga constante para estudiar las propiedades hidráulicas del material. Los resultados indican que es factible producir concreto permeable con agregados sostenibles que cumplan con los estándares y que se podría usar en la construcción de calzadas. Por otro lado, se propone una correlación de permeabilidad y porosidad que involucra las leyes de Bernoulli y Darcy y establece las condiciones de contorno en las que funcionan estas dos propiedades, teniendo como conclusión una ecuación exponencial que caracteriza la eficiencia hidráulica de los canales internos del material relacionado. A la interconexión de poros. Al realizar la regresión no lineal, la ecuación se ajusta a los resultados encontrados y se ajusta a lo que se encuentra en la literatura, siendo una herramienta excelente para identificar la eficiencia hidráulica del material

Hypothalamic sites responding to predator threats - the role of the dorsal premammillary nucleus in unconditioned and conditioned antipredatory defensive behavior

In this study we provide a comprehensive analysis of the hypothalamic activation pattern during exposure to a live predator or an environment previously associated with a predator. Our results support the view that hypothalamic processing of the actual and the contextual predatory threats share the same circuit, in which the dorsal premammillary nucleus (PMd) plays a pivotal role in amplifying this processing. To further understand the role of the PMd in the circuit organizing antipredatory defensive behaviors, we studied rats with cytotoxic PMd lesions during cat exposure and examined the pattern of behavioral responses as well as how PMd lesions affect the neuronal activation of the systems engaged in predator detection, in contextual memory formation and in defensive behavioral responses. Next, we investigated how pharmacological blockade of the PMd interferes with the conditioned behavioral responses to a context previously associated with a predator, and how this blockade affects the activation pattern of periaqueductal gray (PAG) sites likely to organize the conditioned behavioral responses to the predatory context. Behavioral observations indicate that the PMd interferes with both unconditioned and conditioned antipredatory defensive behavior. Moreover, we have shown that the PMd influences the activation of its major projecting targets, i.e. the ventral part of the anteromedial thalamic nucleus which is likely to influence mnemonic processing, and PAG sites involved in the expression of antipredatory unconditioned and conditioned behavioral responses. Of particular relevance, this work provides evidence to elucidate the basic organization of the neural circuits integrating unconditioned and contextual conditioned responses to predatory threats.FAPESP Fundacao de Amparo a Pesquisa do Estado de Sao Paulo[01/14039-9]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP Fundacao de Amparo a Pesquisa do Estado de Sao Paulo[05/59286-4]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)CNPq Conselho Nacional de Desenvolvimento Cientifico e TecnologicoConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPES

Transfusão sangüínea no intra-operatório, complicações e prognóstico Transfusión sanguínea en el intraoperatorio, complicaciones y pronóstico Complications and prognosis of intraoperative blood transfusion

JUSTIFICATIVA E OBJETIVOS: Transfusões sangüíneas no intra-operatório estão associadas a aumento de complicações no pós-operatório e custos hospitalares. Portanto, este estudo avaliou as características, complicações e possíveis fatores de riscos para morte em pacientes cirúrgicos que necessitaram de transfusões sangüíneas no intra-operatório. MÉTODO: Coorte prospectiva, durante período de um ano, no centro cirúrgico de hospital terciário. Incluíram-se pacientes com idade acima de 18 anos que necessitaram de transfusões sangüíneas no intra-operatório. Testemunhas de Jeová, pacientes que receberam transfusões prévias, falência coronariana e lesão encefálica aguda foram excluídos. RESULTADOS: O estudo envolveu 80 pacientes, com idade média de 68,4 ± 14,1 anos. Os pacientes ASA II foram prevalentes com 69,6% dos casos, os escores APACHE II e POSSUM foram em média, respectivamente, 13,6 ± 4,4 e 37,5 ± 11,4. A hemoglobina média no momento da transfusão era 8,2 ± 1,8 g.dL-1 e 19% dos pacientes apresentavam hemoglobina maior que 10 g.dL-1. Os pacientes receberam em média 2,2 ± 0,9 UI de concentrados de hemácias. A mortalidade hospitalar foi 26,3%. As complicações pós-transfusões totalizaram 57,5% dos casos no pós-operatório e a mais freqüente foi infecção. Foram fatores independentes de morte na regressão logística os escores APACHE II (OR = 1,34; IC 95% 1,102 - 1,622), POSSUM (OR = 1,08; IC 95% 1,008 - 1,150) e número de unidades de concentrados de hemácias recebidas (OR = 2,22; IC 95% 1,100 - 4,463). Quanto maior o número de transfusões sangüíneas, maiores as incidências de complicações e mortalidade. CONCLUSÕES: O valor de hemoglobina e o número de unidades de concentrados de hemácias utilizados foram elevados comparados com os estudos que preconizam estratégias restritivas. Foi encontrada nesta amostra alta incidência de complicações, principalmente infecções, e elevada mortalidade. Os escores APACHE II, POSSUM e maior número de transfusões foram fatores de riscos independentes de pior prognóstico no pós-operatório.<br>JUSTIFICATIVA Y OBJETIVOS: Transfusiones sanguíneas en el intraoperatorio están asociadas al aumento de complicaciones en el postoperatorio y costes hospitalarios. Por tanto, este estudio evaluó las características, complicaciones y los posibles factores de riesgos para muerte en pacientes quirúrgicos que necesitaron transfusiones sanguíneas en el intraoperatorio. MÉTODO: Categoría prospectiva, durante el período de un año, en el centro quirúrgico de hospital terciario. Se incluyeron pacientes con edad por encima de los 18 años que necesitaron transfusiones sanguíneas en el intraoperatorio. Testigos de Jeová, pacientes que recibieron transfusiones previas, fracaso coronario y lesión encefálica aguda quedaron excluidos del estudio. RESULTADOS: El estudio involucró a 80 pacientes, con una edad promedio entre los 68,4 ± 14,1 años. Los pacientes ASA II eran prevalecientes con 69,6% de los casos, las puntuaciones APACHE II y POSSUM fueron, como promedio respectivamente de 13,6 ± 4,4 y 37,5 ± 11,4. La hemoglobina promedio al momento de la transfusión era de 8,2 ± 1,8 g.dL-1 y un 19% de los pacientes tuvieron hemoglobina por encima de 10 g.dL-1. Los pacientes recibieron como promedio 2,2 ± 0,9 UI de concentrados de hematíes. La mortalidad hospitalaria fue de un 26,3%. Las complicaciones postransfusiones totalizaron un 57,5% de los casos en el postoperatorio y la más frecuente fue la infección. Fueron factores independientes de muerte en la regresión logística las puntuaciones APACHE II (OR = 1,34; IC 95% 1,102-1,622), POSSUM (OR = 1,08; IC 95% 1,008 - 1,150) y número de unidades de concentrados de hematíes recibidos (OR = 2,22; IC 95% 1,100 - 4,463). Mientras mayor es el número de transfusiones sanguíneas, mayores son las incidencias de las complicaciones y de la mortalidad. CONCLUSIONES: El valor de la hemoglobina y el número de unidades de concentrados de hematíes utilizados fueron elevados comparados con los estudios que preconizan estrategias restrictivas. Fue encontrada en esa muestra una alta incidencia de complicaciones, principalmente infecciones, y una elevada mortalidad. Los puntajes APACHE II, POSSUM y mayor número de transfusiones fueron factores de riesgos independientes de un peor pronóstico en el postoperatorio.<br>BACKGROUND AND OBJECTIVES: Intraoperative blood transfusions are associated with an increase in postoperative complications and hospital costs. Thus, this study evaluated the characteristics, complications, and probable risk factors for death in surgical patients who needed intraoperative blood transfusions. METHODS: This is a prospective study that spanned a one-year period, undertaken at the surgical suite of a tertiary hospital. Patients older than 18 years who needed intraoperative blood transfusions were included in this study. Jehovah witnesses, patients with a history of prior blood transfusions, coronary failure, and acute brain lesions were excluded. RESULTS: Eighty patients with mean age of 68.4 ± 14.1 years participated in the study. Most patients were ASA II, representing 69.6% of the study group; APACHE and POSSUM scores were 13.6 ± 4.4 and 37.5 ± 11.4, respectively. Mean hemoglobin at the time of transfusion was 8.2 ±1.8 g.dL-1 and 19% of the patients had hemoglobin levels higher than 10 g.dL-1. Patients received an average of 2.2 ± 0.9 IU of packed red blood cells. Hospital mortality was 26.3%. Post-transfusion complications totaled 57.5% of the cases in the postoperative period, and most of them were due to infections. In the logistic regression, independent factors for death included APACHE II (OR = 1.34; 95% CI 1.102-1.622), POSSUM (OR = 1.08; 95% CI 1.008-1.150) and the number of packed red blood cells received (OR = 2.22; 95% CI 1.100-4.463). Thus, the higher the number of transfusions, the greater the incidence of complications and mortality. CONCLUSIONS: Hemoglobin level, and the number of packed red blood cells used were elevated when compared with studies that suggest restrictive strategies. This sample presented a high incidence of complications, especially infections, and complications. APACHE II and POSSUM scores and the number of transfusions were independent risk factors for a worse postoperative prognosis