Lipopolysaccharide Inhibits the Channel Activity of the P2X7 Receptor

The purinergic P2X7 receptor (P2X7R) plays an important role during the immune response, participating in several events such as cytokine release, apoptosis, and necrosis. The bacterial endotoxin lipopolysaccharide (LPS) is one of the strongest stimuli of the immune response, and it has been shown that P2X7R activation can modulate LPS-induced responses. Moreover, a C-terminal binding site for LPS has been proposed. In order to evaluate if LPS can directly modulate the activity of the P2X7R, we tested several signaling pathways associated with P2X7R activation in HEK293 cells that do not express the TLR-4 receptor. We found that LPS alone was unable to induce any P2X7R-related activity, suggesting that the P2X7R is not directly activated by the endotoxin. On the other hand, preapplication of LPS inhibited ATP-induced currents, intracellular calcium increase, and ethidium bromide uptake and had no effect on ERK activation in HEK293 cells. In splenocytes-derived T-regulatory cells, in which ATP-induced apoptosis is driven by the P2X7R, LPS inhibited ATP-induced apoptosis. Altogether, these results demonstrate that LPS modulates the activity of the P2X7R and suggest that this effect could be of physiological relevance

Partial permutohedra

Partial permutohedra are lattice polytopes which were recently introduced and studied by Heuer and Striker. For positive integers m and n, the partial permutohedron P(m,n) is the convex hull of all vectors in {0,1,...,n}^m whose nonzero entries are distinct. We study the face lattice, volume and Ehrhart polynomial of P(m,n), and our methods and results include the following. For any m and n, we obtain a bijection between the nonempty faces of P(m,n) and certain chains of subsets of {1,...,m}, thereby confirming a conjecture of Heuer and Striker, and we then use this characterization of faces to obtain a closed expression for the h-polynomial of P(m,n). For any m and n with n ≥ m-1, we use a pyramidal subdivision of P(m,n) to establish a recursive formula for the normalized volume of P(m,n), from which we then obtain closed expressions for this volume. We also use a sculpting process (in which P(m,n) is reached by successively removing certain pieces from a simplex or hypercube) to obtain closed expressions for the Ehrhart polynomial of P(m,n) with arbitrary m and fixed n ≤ 3, the volume of P(m,4) with arbitrary m, and the Ehrhart polynomial of P(m,n) with fixed m ≤ 4 and arbitrary n ≥ m-1

Partial permutohedra

Partial permutohedra are lattice polytopes which were recently introduced and studied by Heuer and Striker [arXiv:2012.09901]. For positive integers m and n, the partial permutohedron P(m,n) is the convex hull of all vectors in {0,1,...,n}^m whose nonzero entries are distinct. We study the face lattice, volume and Ehrhart polynomial of P(m,n), and our methods and results include the following. For any m and n, we obtain a bijection between the nonempty faces of P(m,n) and certain chains of subsets of {1,...,m}, thereby confirming a conjecture of Heuer and Striker. We use this characterization of faces to obtain a closed expression for the h-polynomial of P(m,n). For any m and n with n ≥ m−1, we use a pyramidal subdivision of P(m,n) to establish a recursive formula for the normalized volume of P(m,n), from which we then obtain closed expressions for this volume. We also use a sculpting process (in which P(m,n) is reached by successively removing certain pieces from a simplex or hypercube) to obtain closed expressions for the Ehrhart polynomial of P(m,n) with arbitrary m and fixed n ≤ 3, the volume of P(m,4) with arbitrary m, and the Ehrhart polynomial of P(m,n) with fixed m ≤ 4 and arbitrary n ≥ m−1

Distribución de Aedes aegypti y Aedes albopictus en Guatemala 2016

Los recientes brotes de zika y chikungunya en Guatemala, y el continuo padecimiento de dengue, hacen necesario generar preguntas respecto a la presencia de los vectores de arbovirus, Aedes aegypti y A. albopictus, en este país. Los reportes publicados previamente, señalan la presencia de estos vectores en cuatro departamentos de Guatemala. El objetivo de este estudio fue actualizar los reportes de A. aegypti y A. albopictus en Guatemala para informar con datos robustos a las agencias de salud. Se utilizaron datos del Programa de Enfermedades Transmitidas por Vectores del Ministerio de Salud Pública y Asistencia Social, que contiene principalmente información sobre la presencia de estadios larvales de los vectores. Los sitios de colecta de los mosquitos fueron validados usando herramientas de Sistemas de Información Geográfica, generando mapas de distribución de ambas especies de vectores en todo el país. Los resultados incluyen la presencia de A. aegypti en 21 departamentos y A. albopictus en 11. Aedes aegypti fue reportado en zonas bajas con tolerancias a altas temperaturas (32.3 – 34.8°C), mientras A. albopictus se reportó en zonas con mayor precipitación y en mayores altitudes (2301m). Se concluye en un notable incremento en la distribución de estas dos especies en Guatemala, basados en los informes del primer trimestre 2016 del Programa de Enfermedades Transmitidas por Vectores colectados en época seca. Se discuten la oportunidad de integrar a la academia con los programas actuales de vigilancia epidemiológica para abordar las necesidades de investigación de estos vectores a nivel nacional

Revista Minerva Enero - Marzo 2018

El problema de la propiedad intelectual de las investigaciones realizadas con fondos públicos en el derecho de acceso a la información pública Análisis del límite al principio de máxima publicidad frente a la producción científica de las instituciones públicas Determinación de Mercurio, Cadmio, Plomo y Arsénico en ríos de la zona minera de la subcuenca del Río Titihuapa, Cabañas, El Salvador Prevalencia de maloclusión y necesidad de tratamiento ortodóntico en niños con dentición mixta en cuatro centros escolares salvadoreños utilizando el índice de estética dental durante el año 2015 Monitoreo térmico continuo y discreto del volcán Santa Ana, periodo septiembre 2006 - septiembre 2017, El Salvador C. A. Mitos y máscaras La televisión y su impacto por la transmisión de representaciones culturale

Contribution of common and rare variants to bipolar disorder susceptibility in extended pedigrees from population isolates.

Current evidence from case/control studies indicates that genetic risk for psychiatric disorders derives primarily from numerous common variants, each with a small phenotypic impact. The literature describing apparent segregation of bipolar disorder (BP) in numerous multigenerational pedigrees suggests that, in such families, large-effect inherited variants might play a greater role. To identify roles of rare and common variants on BP, we conducted genetic analyses in 26 Colombia and Costa Rica pedigrees ascertained for bipolar disorder 1 (BP1), the most severe and heritable form of BP. In these pedigrees, we performed microarray SNP genotyping of 838 individuals and high-coverage whole-genome sequencing of 449 individuals. We compared polygenic risk scores (PRS), estimated using the latest BP1 genome-wide association study (GWAS) summary statistics, between BP1 individuals and related controls. We also evaluated whether BP1 individuals had a higher burden of rare deleterious single-nucleotide variants (SNVs) and rare copy number variants (CNVs) in a set of genes related to BP1. We found that compared with unaffected relatives, BP1 individuals had higher PRS estimated from BP1 GWAS statistics (P = 0.001 ~ 0.007) and displayed modest increase in burdens of rare deleterious SNVs (P = 0.047) and rare CNVs (P = 0.002 ~ 0.033) in genes related to BP1. We did not observe rare variants segregating in the pedigrees. These results suggest that small-to-moderate effect rare and common variants are more likely to contribute to BP1 risk in these extended pedigrees than a few large-effect rare variants

Prognosis of Transthyretin Cardiac Amyloidosis Without Heart Failure Symptoms.

BACKGROUND Transthyretin amyloid cardiomyopathy (ATTR-CM) is increasingly recognized as a treatable cause of heart failure (HF). Advances in diagnosis and therapy have increased the number of patients diagnosed at early stages, but prognostic data on patients without HF symptoms are lacking. Moreover, it is unknown whether asymptomatic patients benefit from early initiation of transthyretin (TTR) stabilizers. OBJECTIVES The aim of this study was to describe the natural history and prognosis of ATTR-CM in patients without HF symptoms. METHODS Clinical characteristics and outcomes of patients with ATTR-CM without HF symptoms were retrospectively collected at 6 international amyloidosis centers. RESULTS A total of 118 patients (78.8% men, median age 66 years [IQR: 53.8-75 years], 68 [57.6%] with variant transthyretin amyloidosis, mean left ventricular ejection fraction 60.5% ± 9.9%, mean left ventricular wall thickness 15.4 ± 3.1 mm, and 53 [45%] treated with TTR stabilizers at baseline or during follow-up) were included. During a median follow-up period of 3.7 years (IQR: 1-6 years), 38 patients developed HF symptoms (23 New York Heart Association functional class II and 14 functional class III or IV), 32 died, and 2 required cardiac transplantation. Additionally, 20 patients received pacemakers, 13 developed AF, and 1 had a stroke. Overall survival was 96.5% (95% CI: 91%-99%), 90.4% (95% CI: 82%-95%), and 82% (95% CI: 71%-89%) at 1, 3, and 5 years, respectively. Treatment with TTR stabilizers was associated with improved survival (HR: 0.31; 95% CI: 0.12-0.82; P = 0.019) and remained significant after adjusting for sex, age, ATTR-CM type, and estimated glomerular filtration rate (HR: 0.18; 95% CI: 0.06-0.55; P = 0.002). CONCLUSIONS After a median follow-up period of 3.7 years, 1 in 3 patients with asymptomatic ATTR-CM developed HF symptoms, and nearly as many died or required cardiac transplantation. Treatment with TTR stabilizers was associated with improved prognosis.This work was supported by grants from Instituto de Salud Carlos III (PI18/0765 and PI20/01379). Dr Gonzalez-Lopez has received speaker fees from Pfizer and Alnylam; has received consulting fees from Pfizer and Proclara; and has received research and educational support to her institution from Pfizer, BridgeBio, and Alnylam. Dr Obici has received speaker and consulting fees from Pfizer, Alnylam, and Akcea. Dr AbouEzzeddine has received research grant support from Pfizer. Dr Mussinelli has received speaker fees from Pfizer and Akcea. Dr Dispenzieri has received consulting fees from Janssen and Akcea; and has received research support from Pfizer, Alnylam, Celgene, and Takeda. Dr Perlini has received speaker and consulting fees from Pfizer, Alnylam, and Akcea. Dr Palladini has received speaker fees from Janssen-Cilag, Pfizer, and Siemens; and has participated on an advisory board for Janssen Cilag. Dr Damy has received research grants or consulting fees from Alnylam, Akcea, Pfizer, and Prothena. Dr Grogan has received research grant support and consulting fees to her institution from Alnylam, Eidos, Pfizer, and Prothena. Dr Maurer has received grant support from National Institutes of Health (R01HL139671-01, R21AG058348, and K24AG036778); has received consulting income from Pfizer, GlaxoSmithKline, Eidos, Prothena, Akcea, and Alnylam; and has received clinical trial funding to his institution from Pfizer, Prothena, Eidos, and Alnylam. Dr Garcia-Pavia has received speaker fees from Pfizer, BridgeBio, Alnylam, and Ionis; has received consulting fees from Pfizer, BridgeBio, AstraZeneca, NovoNordisk, Neuroimmune, Alnylam, Alexion, and Attralus; and has received research and educational support to his institution from Pfizer, BridgeBio, and Alnylam. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.S

A randomized study of nutritional supplementation in patients with unilateral wet age-related macular degeneration

The purpose of this study is evaluate the efficacy and safety of medicinal products con-taining the original Age-Related Eye Disease group (AREDS) formulation at doses approved in Europe (EU, control group; n = 59) with a product that adds DHA, lutein, zeaxanthin, resveratrol and hydroxytyrosol to the formula (intervention group; n = 50). This was a multicenter, random-ized, observer-blinded trial conducted in patients aged 50 years or older diagnosed with unilateral exudative Age related Macular Degeneration AMD. At month 12, the intervention did not have a significant differential effect on visual acuity compared with the control group, with an estimated treatment difference in Early Treatment Diabetic Retinopathy Study (ETDRS) of -1.63 (95% CI -0.83 to 4.09; p = 0.192). The intervention exhibited a significant and, in most cases, relevant effect in terms of a reduction in some inflammatory cytokines and a greater improvement in the fatty acid profile and serum lutein and zeaxantin concentration. In patients with unilateral wet AMD, the addition of lutein, zeaxanthin, resveratrol, hydroxytyrosol and DHA to the AREDS EU recommended doses in the short-term did not have a differential effect on visual acuity compared to a standard AREDS EU formula but, in addition to improving the fatty acid profile and increasing carotenoid serum levels, may provide a beneficial effect in improving the proinflammatory and proangiogenic profile of patients with AMD. © 2021 by the authors. Licensee MDPI, Basel, Switzerland