In vivo activity of plant-based interleukin-12 in the lung of Balb/c mouse

<p>Abstract</p> <p>Background</p> <p>In the last years, plants are being used for the production of a wide variety of biopharmaceuticals, including cytokines, and have the potential to serve as vehicles for mucosal administration of these molecules. We had previously reported the expression of a cytokine, interleukin-12 (IL-12), in transgenic tomato plants and had demonstrated that it retained its biologic activity <it>in vitro</it>.</p> <p>Findings</p> <p>In this work, we administered crude extracts of IL-12-containing tomato fruits to mice through the intratracheal route, measuring endogenous IL-12 and determining biologic activity by quantification of interferon-gamma (IFN-γ) in lungs and by histological analysis. IFN-γ expression in lungs, as well as histological analysis, indicate that tomato-expressed IL-12 retains its biologic activity and, most importantly, its effects are restricted to the site of administration.</p> <p>Conclusion</p> <p>Our results indicate that the functional activity of tomato-expressed IL-12 is comparable to that of commercial recombinant IL-12 when given via the mucosal route. This opens the possibility of using crude extracts prepared from tomatoes expressing IL-12 for certain immunotherapies.</p

Epistatic interaction of ERAP1 and HLA-B in Behçet disease: a replication study in the Spanish population

Behçet's disease (BD) is a multifactorial disorder associated with the HLA region. Recently, the ERAP1 gene has been proposed as a susceptibility locus with a recessive model and with epistatic interaction with HLA-B51. ERAP1 trims peptides in the endoplasmic reticulum to optimize their length for MHC-I binding. Polymorphisms in this gene have been related with the susceptibility to other immune-mediated diseases associated to HLA class I. Our aim was, the replication in the Spanish population of the association described in the Turkish population between ERAP1 (rs17482078) and BD. Additionally, in order to improve the understanding of this association we analyzed four additional SNPs (rs27044, rs10050860, rs30187 and rs2287987) associated with other diseases related to HLA class I and the haplotype blocks in this gene region. According to our results, frequencies of the homozygous genotypes for the minor alleles of all the SNPs were increased among patients and the OR values were higher in the subgroup of patients with the HLA-B risk factors, although differences were not statistically significant. Moreover, the presence of the same mutation in both chromosomes increased the OR values from 4.51 to 10.72 in individuals carrying the HLA-B risk factors. Therefore, although they were not statistically significant, our data were consistent with an association between ERAP1 and BD as well as with an epistatic interaction between ERAP1 and HLA-B in the Spanish population

Vacuna tetravalente de influenza en los programas nacionales de inmunización para los países de América Latina

Since 2012-2013 influenza season, World Health Organization (who) recommends the formulation of tetravalent vaccines. Globally, many countries already use tetravalent vaccines in their national immunization programs, while in Latin America only a small number. Two Influenza b lineages co-circulate, their epidemiological behavior is unpredictable. On average they represent 22.6% of influenza cases and more than 50% in predominant seasons. The lack of concordance between recommended and circulating strains was 25 and 32% in the 2010-2017 and 2000-2013 seasons, respectively. There are no clinical differences between influenza A and B. It occurs more frequently from five to 19 years of age. Influenza b has a higher proportion of attributable deaths than influenza a (1.1 vs. 0.4%), or 2.65 (95% ci 1.18-5.94). A greater number of hospitalizations when the strains mismatch (46.3 vs. 28.5%; p <.0001). Different evaluations have demonstrated its cost effectiveness. The compilation of this information supports the use of quadrivalent vaccines in Latin American countries.Revisión por pare

Clima, variabilidad y cambio climático en la Vertiente Caribe de Costa Rica: Un estudio básico para la actividad bananera

informe de investigación -- Universidad de Costa Rica. Centro de Investigaciones Geofísicas, 2013. Forma de citar el trabajo: Amador, J. A., E. J. Alfaro, H. G. Hidalgo, F. J. Soley, F. Solano, J. L. Vargas, F. Sáenz, B. Calderón, P. M. Pérez, J. J. Vargas, R. Díaz, A. Goebel, A. Montero, J. L. Rodríguez, A. Salazar, P. Ureña, N. Mora, I. Rivera, C. Vega y C. Bojorge, 2013. Clima, variabilidad y cambio climático en la Vertiente Caribe de Costa Rica: Un estudio básico para la actividad bananera. Informe Final del Proyecto VI-805-B0-402. Centro de Investigaciones Geofísicas (CIGEFI), Vicerrectoría de Investigación y Escuela de Física, Universidad de Costa Rica y Corporación Bananera Nacional (CORBANA), Setiembre 2013, 225 pp.Este Informe Final (IF) describe en forma sintética, los alcances y productos del proyecto “Clima, variabilidad y cambio climático en la Vertiente Caribe de Costa Rica: Un estudio básico para la actividad bananera”, en relación con el cumplimiento, por parte del Centro de Investigaciones Geofísicas (CIGEFI) de la Universidad de Costa Rica (UCR), de las Especificaciones y Requisitos Técnicos (ERT) de la investigación contratada con la Corporación Bananera Nacional (CORBANA). Los ERT de CORBANA (ERTC) están contenidos en la Parte 7 de la Propuesta Original entregada a la Corporación en octubre de 2010. Los detalles de los productos son discutidos en las diferentes secciones del IF. En este sentido, se examinaron la Estructura y Funcionalidad de la Base de Datos (BANACLIMA) y la Red de Estaciones de la Corporación. Se destaca, entre otras cosas, la implementación, en colaboración con CORBANA, de una torre de observación meteorológica en Siquirres (CIGEFI_et) con instrumental de precipitación, temperatura, viento y humedad, instalado a 10, 20 y 30 m de altura, con complemento de presión, temperatura y humedad (del suelo) en superficie. Se generaron y entregaron, tanto en formato JPEG o similar y en un Sistema de Información Geográfica (SIG) productos de climatología regional derivados de la información de BANACLIMA y de bases de datos regionales. Los productos entregados en el SIG facilitan el uso aplicado de la información. Este proceso contempló la familiarización de personal con los productos generados y no formaba parte de los ERTC. Se entregan clasificaciones climáticas basadas en los métodos de Thornthwaite y Hargreaves, con amplias discusiones sobre su aplicación y limitaciones. Las climatologías generadas con base al modelo MM5 incluyen aspectos de variabilidad que toma en cuenta los modos globales de El Niño Oscilación del Sur (ENOS), la Oscilación Multidecadal del Atlántico (OMDA), ambos basados en índices de la temperatura superficial del océano como predictor de la variabilidad atmosférica regional. Se analizaron datos atmosféricos regionales para obtener indicativos del cambio climático observado para varias variables troposféricas, entre ellas temperatura superficial y precipitación. Un tema investigado en este proyecto y no contemplado tampoco en las ERTC, es la inclusión de algunas proyecciones futuras sobre el cambio climático en la región de interés, basado en resultados de modelos de circulación general (conocidos como 20c3m runs) para el Informe de 2010 del Panel Inter-Gubernamental para el Cambio Climático. Otro aspecto, no contemplado en las ERTC, es la recolección de importantes datos históricos sobre meteorología y el desarrollo institucional de la Corporación. Sobre este tema, el CIGEFI espera continuar investigando por su parte y de darse las condiciones de acceso requeridas, dotar en un futuro a CORBANA de un documento más completo sobre su historia y el desarrollo en la actividad bananera nacional. Personal de CORBANA participó en Mini-congresos, talleres y presentaciones del CIGEFI en relación con los temas e investigaciones realizadas para el proyecto. Personal del Centro participó en Congresos Bananeros, talleres y seminarios dando a conocer los resultados del proyecto con CORBANA. Un importante grupo de artículos han sido publicados, otros están en proceso, todos ellos mostrando los productos y resultados de la investigación. Con respecto a los diferentes aspectos que tiene que ver con las ERTC, se incorporaron recomendaciones específicas, en el Informe Primero (IP), de setiembre de 2011, en el Informe Segundo (IS), de mayo de 2012 y en el presente IF. En este IF se incorporan figuras o tablas que aparecen en el IP o en el IS, sin embargo, éstas fueron, en general, mejoradas tanto por el uso de información complementaria, cambio o mejoramiento del método de trabajo o para incorporar un periodo más extenso de datos.Corporación Bananera Nacional (CORBANA). Universidad de Costa Rica (UCR).UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigaciones Geofísicas (CIGEFI

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants

Background Hypertension can be detected at the primary health-care level and low-cost treatments can effectively control hypertension. We aimed to measure the prevalence of hypertension and progress in its detection, treatment, and control from 1990 to 2019 for 200 countries and territories. Methods We used data from 1990 to 2019 on people aged 30–79 years from population-representative studies with measurement of blood pressure and data on blood pressure treatment. We defined hypertension as having systolic blood pressure 140 mm Hg or greater, diastolic blood pressure 90 mm Hg or greater, or taking medication for hypertension. We applied a Bayesian hierarchical model to estimate the prevalence of hypertension and the proportion of people with hypertension who had a previous diagnosis (detection), who were taking medication for hypertension (treatment), and whose hypertension was controlled to below 140/90 mm Hg (control). The model allowed for trends over time to be non-linear and to vary by age. Findings The number of people aged 30–79 years with hypertension doubled from 1990 to 2019, from 331 (95% credible interval 306–359) million women and 317 (292–344) million men in 1990 to 626 (584–668) million women and 652 (604–698) million men in 2019, despite stable global age-standardised prevalence. In 2019, age-standardised hypertension prevalence was lowest in Canada and Peru for both men and women; in Taiwan, South Korea, Japan, and some countries in western Europe including Switzerland, Spain, and the UK for women; and in several low-income and middle-income countries such as Eritrea, Bangladesh, Ethiopia, and Solomon Islands for men. Hypertension prevalence surpassed 50% for women in two countries and men in nine countries, in central and eastern Europe, central Asia, Oceania, and Latin America. Globally, 59% (55–62) of women and 49% (46–52) of men with hypertension reported a previous diagnosis of hypertension in 2019, and 47% (43–51) of women and 38% (35–41) of men were treated. Control rates among people with hypertension in 2019 were 23% (20–27) for women and 18% (16–21) for men. In 2019, treatment and control rates were highest in South Korea, Canada, and Iceland (treatment >70%; control >50%), followed by the USA, Costa Rica, Germany, Portugal, and Taiwan. Treatment rates were less than 25% for women and less than 20% for men in Nepal, Indonesia, and some countries in sub-Saharan Africa and Oceania. Control rates were below 10% for women and men in these countries and for men in some countries in north Africa, central and south Asia, and eastern Europe. Treatment and control rates have improved in most countries since 1990, but we found little change in most countries in sub-Saharan Africa and Oceania. Improvements were largest in high-income countries, central Europe, and some upper-middle-income and recently high-income countries including Costa Rica, Taiwan, Kazakhstan, South Africa, Brazil, Chile, Turkey, and Iran. Interpretation Improvements in the detection, treatment, and control of hypertension have varied substantially across countries, with some middle-income countries now outperforming most high-income nations. The dual approach of reducing hypertension prevalence through primary prevention and enhancing its treatment and control is achievable not only in high-income countries but also in low-income and middle-income settings

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Central America [in State of the Climate in 2014]

Most of the dozens of essential climate variables monitored each year in this report continued to follow their long-term trends in 2014, with several setting new records. Carbon dioxide, methane, and nitrous oxide the major greenhouse gases released into Earth’s atmosphere once again all reached record high average atmospheric concentrations for the year. Carbon dioxide increased by 1.9 ppm to reach a globally aver- aged value of 397.2 ppm for 2014. Altogether, 5 major and 15 minor greenhouse gases contributed 2.94 W m-2 of direct radiative forcing, which is 36% greater than their contributions just a quarter century ago. Accompanying the record-high greenhouse gas concen- trations was nominally the highest annual global surface temperature in at least 135 years of modern record keeping, according to four independent observational analyses. The warmth was distributed widely around the globe's land areas, Europe observed its warmest year on record by a large margin, with close to two dozen countries breaking their previous national temperature records; many countries in Asia had an- nual temperatures among their 10 warmest on record; Africa reported above-average temperatures across most of the continent throughout 2014; Australia saw its third warmest year on record, following record heat there in 2013; Mexico had its warmest year on record; and Argentina and Uruguay each had their second warmest year on record. Eastern North America was the only major region to observe a below-average annual temperature.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigaciones Geofísicas (CIGEFI

Cytotoxic bioactivity of some phenylpropanoic acid derivatives

In this study, we synthesized a series of phenylpropanoic acid derivatives based on modifications at four selected points of the molecular scaffold. The in vitro antiproliferative activities of the compounds were examined in representative human solid tumor cell lines. A SAR was established pointing out the relevance of the substituents. The best activity profiles were obtained for the derivatives bearing more lipophilic esters (GI50 3.1-21 μM).Fil: Reta, Guillermo Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Tonn, Carlos Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Ríos Luci, Carla. Universidad de La Laguna; EspañaFil: León, Leticia G.. Universidad de La Laguna; EspañaFil: Pérez Roth, Eduardo. Universidad de La Laguna; EspañaFil: Padrón, José M.. Universidad de La Laguna; EspañaFil: Donadel, Osvaldo Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; Argentin