Comparative assessment of biologics in treatment of psoriasis: drug design and clinical effectiveness of ustekinumab

The development of psoriasis and psoriatic arthritis is a multistep process that leads to chronic or recurrent inflammation. Recent studies have suggested the importance of T helper (TH)1 and TH17 cells, accessory cells, and proinflammatory cytokines in the pathogenesis of the enthesis, synovium, and skin involvement in psoriasis in the presence of susceptibility genes that remain quiescent until triggered. Biologics, such as soluble CTLA-4 immunoglobulin, tumor necrosis factor (TNF) inhibitors, and ustekinumab, inhibit T cell activation which eventually leads to further stimulation of the interleukin 12, 17, and 23 axis, TNF-α, and lymphotoxin-α. Treatment with TNF-α blockers has been effective in refractory psoriasis and psoriatic arthritis, but there is still a subgroup of patients who do not respond to TNF inhibitors and, paradoxically, when treated, may develop TNF-induced psoriasis. Ustekinumab, because of its different mechanism of action at the level of the interleukin 12, 17, and 23 pathways, is an alternative treatment for this group of patients

Fasciolosis en familiares de pacientes con infección por Fasciola hepatica en el Perú

High prevalence rates of human fascioliasis have been described in several regions of Peru. We surveyed 20 families in an endemic area of Peru in order to determine the proportion of infection with F. hepatica in relatives of diagnosed subjects and in order to identify associated risk factors. The study included feces and blood samples of 93 subjects. Ages ranged from one to 53 (mean = 18.6; SD = 14.2). The overall prevalence of fascioliasis by fecal examinations was 33.3% (n = 83) and by serology, 51.9% (n = 86). The prevalence in age group I (; 19 years old) 15.4% and 37.5%. The main associated risk factor with fascioliasis was eating salads (OR = 3.29, CI = 1.2 - 9.0, p = 0.02). In conclusion, human fascioliasis is highly prevalent in the relatives of index cases and the most significant risk factor of acquiring fascioliasis in the family is eating salads in endemic areas.Altas tasas de fasciolosis humana han sido descritas en varias regiones del Perú. Estudiamos 20 familias en una área endémica del Perú para determinar la proporción de infección con F. hepatica en los familiares de los sujetos diagnosticados y para identificar factores de riesgo asociados. El estudio incluyó un total de 93 sujetos, quienes contribuyeron con muestras de heces y sangre. Las edades comprendieron desde 1 a 53 años (media = 18.6; DS = 14.2). La prevalencia general de fasciolosis por exámenes de heces fue 33.3% (n = 83) y por serología, 51.9% (n = 86). La prevalencia en el grupo de edad I (; 19 años de edad) 15.4% y 37.5%. El principal factor de riesgo asociado con fasciolosis fue comer ensaladas (OR = 3.29, IC = 1.2-9.0, p = 0.02). En conclusión, la fasciolosis humana es altamente prevalente en familiares de los casos índices y el factor de riesgo más significante para adquirirla en la familia es comer ensaladas en las áreas endémicas

The ordered weighted average inflation

This paper introduces the ordered weighted average inflation (OWAI). The OWAI operator aggregates the information of a set of inflations and provides a range of scenarios from the minimum and the maximum inflation. The advantage of this approach is that it can provide a flexible inflation formula that can be adapted to the specific characteristics of the enterprise, region, state or country (...

The Netrin-4/ Neogenin-1 axis promotes neuroblastoma cell survival and migration

Neogenin-1 (NEO1) is a transmembrane receptor involved in axonal guidance, angiogenesis, neuronal cell migration and cell death, during both embryonic development and adult homeostasis. It has been described as a dependence receptor, because it promotes cell death in the absence of its ligands (Netrin and Repulsive Guidance Molecule (RGM) families) and cell survival when they are present. Although NEO1 and its ligands are involved in tumor progression, their precise role in tumor cell survival and migration remain unclear. Public databases contain extensive information regarding the expression of NEO1 and its ligands Netrin-1 (NTN1) and Netrin-4 (NTN4) in primary neuroblastoma (NB) tumors. Analysis of this data revealed that patients with high expression levels of both NEO1 and NTN4 have a poor survival rate. Accordingly, our analyses in NB cell lines with different genetic backgrounds revealed that knocking-down NEO1 reduces cell migration, whereas silencing of endogenous NTN4 induced cell death. Conversely, overexpression of NEO1 resulted in higher cell migration in the presence of NTN4, and increased apoptosis in the absence of ligand. Increased apoptosis was prevented when utilizing physiological concentrations of exogenous Netrin-4. Likewise, cell death induced after NTN4 knock-down was rescued when NEO1 was transiently silenced, thus revealing an important role for NEO1 in NB cell survival. In vivo analysis, using the chicken embryo chorioallantoic membrane (CAM) model, showed that NEO1 and endogenous NTN4 are involved in tumor extravasation and metastasis. Our data collectively demonstrate that endogenous NTN4/NEO1 maintain NB growth via both pro-survival and pro-migratory molecular signaling.Veronica Palma's work was supported by FONDECYT-1140697. Andrea A. Villanueva, Paulina Falcon and Luis Solano were beneficiaries of CONICYT Fellowships for PhD studies (21130521, AV; 21120358, PF; 21110302, LS).S

Factors behind the success story of under-five stunting in Peru: a district ecological multilevel analysis

Background: Stunting prevalence in children less than 5 years has remained stagnated in Peru from 1992 to 2007, with a rapid reduction thereafter. We aimed to assess the role of different predictors on stunting reduction over time and across departments, from 2000 to 2012. Methods: We used various secondary data sources to describe time trends of stunting and of possible predictors that included distal to proximal determinants. We determined a ranking of departments by annual change of stunting and of different predictors. To account for variation over time and across departments, we used an ecological hierarchical approach based on a multilevel mixed-effects regression model, considering stunting as the outcome. Our unit of analysis was one department-year. Results: Stunting followed a decreasing trend in all departments, with differing slopes. The reduction pace was higher from 2007–2008 onwards. The departments with the highest annual stunting reduction were Cusco (−2.31%), Amazonas (−1.57%), Puno (−1.54%), Huanuco (−1.52%), and Ancash (−1.44). Those with the lowest reduction were Ica (−0.67%), Ucayali (−0.64%), Tumbes (−0.45%), Lima (−0.37%), and Tacna (−0.31%). Amazon and Andean departments, with the highest baseline poverty rates and concentrating the highest rural populations, showed the highest stunting reduction. In the multilevel analysis, when accounting for confounding, social determinants seemed to be the most important factors influencing annual stunting reduction, with significant variation between departments. Conclusions: Stunting reduction may be explained by the adoption of anti-poverty policies and sustained implementation of equitable crosscutting interventions, with focus on poorest areas. Inclusion of quality indicators for reproductive, maternal, neonatal and child health interventions may enable further analyses to show the influence of these factors. After a long stagnation period, Peru reduced dramatically its national and departmental stunting prevalence, thanks to a combination of social determinants and crosscutting factors. This experience offers useful lessons to other countries trying to improve their children’s nutrition.Revisión por pare

Optical Photometry of the Type Ia SN 1999ee and the Type Ib/c SN 1999ex in IC 5179

We present UBVRIz lightcurves of the Type Ia SN 1999ee and the Type Ib/c SN 1999ex, both located in the galaxy IC 5179. SN 1999ee has an extremely well sampled lightcurve spanning from 10 days before Bmax through 53 days after peak. Near maximum we find systematic differences ~0.05 mag in photometry measured with two different telescopes, even though the photometry is reduced to the same local standards around the supernova using the specific color terms for each instrumental system. We use models for our bandpasses and spectrophotometry of SN 1999ee to derive magnitude corrections (S-corrections) and remedy this problem. This exercise demonstrates the need of accurately characterizing the instrumental system before great photometric accuracies of Type Ia supernovae can be claimed. It also shows that this effect can have important astrophysical consequences since a small systematic shift of 0.02 mag in the B-V color can introduce a 0.08 mag error in the extinction corrected peak B magnitudes of a supernova and thus lead to biased cosmological parameters. The data for the Type Ib/c SN 1999ex present us with the first ever observed shock breakout of a supernova of this class. These observations show that shock breakout occurred 18 days before Bmax and support the idea that Type Ib/c supernovae are due to core collapse of massive stars rather than thermonuclear disruption of white dwarfs.Comment: 55 pages, 15 figures, accepted by the Astronomical Journa

Effect of Activated Carbon Made from Cocoa (Theobroma Cacao L.) Shells on the Adsorption of Iron in Aquifer Water

This research aims to determine the effect of activated carbon obtained from cocoa husks (Theobroma cacao L.) on the adsorption of iron (II) present in water of an aquifer for human consumption. Charcoal was prepared at different carbonization temperatures (500, 600 and 700 °C) for 30 minutes and activated with phosphoric acid in the proportions of 1:1. Iron (II) adsorption was determined as a function of variations in mixing speed, contact time, charcoal dosage and stirring speed. It was determined that, over the range considered, agitation speeds had no significant effect on the percentage of iron (II) removal, being the dose of activated carbon and temperature, the most influential variables. The water samples had an initial iron concentration of 3.15 mg/L and 4 mg/L. The best iron (II) adsorption result was obtained with activated carbon at the carbonization temperature of 700 °C, with a mass of 1.5 g of carbon, with efficiencies of 93 % and 98 % for both samples considered. Based on the results, it was concluded water for human consumption is treatable with activated carbon derived from Theobroma cacao L. for the adsorption of iron (II), considering that this parameter is below the maximum limit of 0.3 mg/L allowed by current regulations

Growth, development and concentration of macronutrients in coffee genotypes (coffea robusta P.) with different doses of organic fertilizer

El café es un cultivo de importancia social y comercial, se estima que es el sustento de 25 millones de familias en las regiones tropicales y subtropicales del mundo. Con el objetivo de evaluar el crecimiento, desarrollo y concentración de macronutrientes en genotipos de café con diferentes dosis de abono orgánico se realizó un ensayo en el centro experimental Sacha Wiwa, bajo un diseño de bloques aleatorios con arreglo factorial (genotipos x dosis de abono orgánico Bioabor®). Las variables que se midieron fueron altura de planta, diámetro del tallo, concentración y relación de macronutrientes en el tejido foliar, análisis físico y químico del suelo al inicio y final del estudio. Los datos fueron analizados con estadística descriptiva univariante y técnicas paramétricas. Para la comparación entre medias se empleó el test Tukey al 95% de probabilidad. La variedad Ecorobusta fue la que obtuvo la mayor altura y diámetro de tallo. El abono orgánico inhibe el crecimiento y desarrollo del cultivo de café. Las dosis de abono a 1000, 1500 y 2000 kg /ha aplicada en este orden en la variedad NapoPayomino, Ecorobusta y Conilón reducen la concentración de N en el tejido foliar. Se encontró una correlación positiva significativa entre la altura de planta y diámetro del tallo.Coffee is a crop of social, economic and commercial importance, it is estimated that it is the livelihood of millions of families in the tropical and subtropical regions of the world. In order to evaluate the growth, development and concentration of macronutrients in coffee genotypes with different doses of organic fertilizer, a trial was carried out at the Sacha Wiwa experimental center, under a random block design with factorial arrangement (A) genotypes (B) fertilizer dose. The variables that were measured were plant height, stem diameter, concentration and ratio of macronutrients in the foliar tissue, physical and chemical analysis of the soil at the beginning and end of the study. The data were analyzed with univariate descriptive statistics and parametric techniques. For the comparison between means, the Tukey test was used at 95% probability. The ecorobusta variety was the one that obtained the highest height and stem diameter. Organic compost inhibits the growth and development of the coffee crop. The doses of fertilizer at 1000, 1500 and 2000 kg BBQ / ha applied in this order in the napopayomino, ecorobusta and conilón varieties reduce the concentration of N in the leaf tissue. A significant positive correlation was found between plant height and stem diameter