A Fatal Case of Generalized Lysosomal Storage Disease in an Infant.

Gangliosidoses are a heterogeneous group of lysosomal storage diseases with an autosomal recessive trait, which are characterized by the intracellular accumulation of gangliosides in several tissues, mainly in neurons. This condition causes a progressive neurodegenerative disorder with varied clinical presentations. Depending on the severity of the enzymatic defect, gangliosidoses show different rates of clinical progression and organ involvement; poor residual enzyme activity is seen in more aggressive forms (infantile and juvenile subtypes) leading to early death whereas cases with better residual enzyme activity have a late onset in adult life and a milder clinical course. Autopsy findings of a 7 month-old girl with histological and ultrastructural changes consistent with gangliosidosis are presented

Determinación de la incertidumbre del método de análisis de aflatoxinas por HPLC en pasa de uva

Objective: This work presents the definition of uncertainties for the methods of analysis of aflatoxins B1, B2, G1 and G2 in raisins by HPLC-FLD. The uncertainty of a method is one of the parameters required by the norm IRAM 301-ISO/IEC 17025:2005Standard, applicable in the Argentine Republic and accredited by the Argentine Accreditation Organism (OAA), and forms part of the validation of analytical methods. In addition, it is a necessary requirement to expand the scope of accreditation of the Laboratory of Analysis of Regional Products of Chemical Engineering (LAPRIQ, by the name in Spanish), belonging to the Institute of Chemical Engineering of the National University of San Juan. Methodology: The procedure used is called “Bottom up”, based on a succession of calculation that take into account  errors from each of the analytical operations decomposed in primary activities. For the initial stage, sources of error that can affect the result of the analysis were identified. The Ishikawa's fishbone procedure was used as a basis for determining the sources of error and their incidence in the final uncertainty of the process. Once the factors that add up to the error in the measurement were defined, all the HPLC calibration tests were performed. Second, the combined uncertainties were added, weighted according to the importance of their contribution through the sensitivity coefficient. Finally, the expanded uncertainty was determined using a coverage factor K = 2, which implies a confidence percentage of 95%. With this factor we can expect to include the largest fraction of the distribution of the values attributed to the measurand. Results: Six sources of error were detected and correspond, on the one hand, to the mass measurements of the sample, extraction volumes, elution, and aliquot for “clean up” and,  on the other, HPLC detection and recovery rate of the method. The calculated uncertainties for the four aflatoxins are AFB1= 0.7 mg/kg, AFB2= 0.2 mg/kg, AFG1 = 0.9 mg/kg y AFG2 = 0.3 mg/kg. Conclusions: The values of the expanded uncertainties are reported in the certificate of analysis, along with the result of the HPLC test, as one of the tests of the validation of the method validation.Contexto: En este trabajo se presenta la determinación de las incertidumbres de los métodos de análisis de aflatoxinas B1, B2, G1 y G2 en pasa de uva por HPLC-FLD. La incertidumbre de un método es uno de los parámetros requeridos por la norma IRAM 301-ISO/IEC 17025:2005, de aplicación en la República Argentina y acreditada por el Organismo Argentino de Acreditación (OAA). Forma parte de la validación del método analítico. Es un requisito necesario para ampliar el alcance de acreditación del Laboratorio de Análisis de Productos Regionales de Ingeniería Química (LAPRIQ), perteneciente al Instituto de Ingeniería Química de la Universidad Nacional de San Juan. Metodología: El procedimiento utilizado es el denominado bottom up, basado en una sucesión de etapas de cálculo que tienen en cuenta los errores provenientes de cada una de las operaciones analíticas descompuestas en actividades primarias. La etapa inicial consiste en la identificación de las fuentes de error que pueden afectar el resultado del análisis. Se tomño como base para la determinación de las fuentes de error, y su incidencia en la incertidumbre final del proceso, el procedimiento de espina de pescado de Ishikawa. Definidos los factores que suman al error en la medición, se realizaron todos los ensayos de calibración del HPLC, índice de recuperación y verificación del instrumental para la determinación de la incertidumbre estándar de los subcomponentes. Se calculó luego la incertidumbre combinada teniendo en cuenta los aportes individuales. Posteriormente se sumaron las incertidumbres combinadas, ponderadas según la importancia de su contribución a través del coeficiente de sensibilidad. Por último, se determinó la incertidumbre expandida usando un factor de cobertura K = 2, que implica un porcentaje de confianza del 95 %. Con este factor se puede esperar que se incluya la mayor fracción de la distribución de los valores atribuidos al mesurando. Resultados: Se detectaron seis fuentes de error, correspondientes a las mediciones de: masa de la muestra, volúmenes de extracción, elución y alícuota para clean up, detección en HPLC e índice de recuperación del método. Las incertidumbres expandidas calculadas de las cuatro aflatoxinas son AFB1= 0,7mg/kg, AFB2= 0,2mg/kg, AFG1 = 0,9 mg/kg y AFG2 = 0,3 mg/kg. Conclusiones: Los valores de las incertidumbres expandidas se informan en el certificado de análisis, junto con el resultado del ensayo por HPLC, como una de las pruebas de la validación del método

Determinación de la incertidumbre del método de análisis de aflatoxinas por HPLC en pasa de uva

Contexto: En este trabajo se presenta la determinación de las incertidumbres de los métodos de análisis de aflatoxinas B1, B2, G1 y G2 en pasa de uva por HPLC-FLD. La incertidumbre de un método es uno de los parámetros requeridos por la norma IRAM 301-ISO/IEC 17025:2005, de aplicación en la República Argentina y acreditada por el Organismo Argentino de Acreditación (OAA). Forma parte de la validación del método analítico. Es un requisito necesario para ampliar el alcance de acreditación del Laboratorio de Análisis de Productos Regionales de Ingeniería Química (LAPRIQ), perteneciente al Instituto de Ingeniería Química de la Universidad Nacional de San Juan. Metodología: El procedimiento utilizado es el denominado bottom up, basado en una sucesión de etapas de cálculo que tienen en cuenta los errores provenientes de cada una de las operaciones analíticas descompuestas en actividades primarias. La etapa inicial consiste en la identificación de las fuentes de error que pueden afectar el resultado del análisis. Se tomño como base para la determinación de las fuentes de error, y su incidencia en la incertidumbre final del proceso, el procedimiento de espina de pescado de Ishikawa. Definidos los factores que suman al error en la medición, se realizaron todos los ensayos de calibración del HPLC, índice de recuperación y verificación del instrumental para la determinación de la incertidumbre estándar de los subcomponentes. Se calculó luego la incertidumbre combinada teniendo en cuenta los aportes individuales. Posteriormente se sumaron las incertidumbres combinadas, ponderadas según la importancia de su contribución a través del coeficiente de sensibilidad. Por último, se determinó la incertidumbre expandida usando un factor de cobertura K = 2, que implica un porcentaje de confianza del 95 %. Con este factor se puede esperar que se incluya la mayor fracción de la distribución de los valores atribuidos al mesurando. Resultados: Se detectaron seis fuentes de error, correspondientes a las mediciones de: masa de la muestra, volúmenes de extracción, elución y alícuota para clean up, detección en HPLC e índice de recuperación del método. Las incertidumbres expandidas calculadas de las cuatro aflatoxinas son AFB1= 0,7mg/kg, AFB2= 0,2mg/kg, AFG1 = 0,9 mg/kg y AFG2 = 0,3 mg/kg. Conclusiones: Los valores de las incertidumbres expandidas se informan en el certificado de análisis, junto con el resultado del ensayo por HPLC, como una de las pruebas de la validación del método

Gut microbial composition and functionality of school-age Mexican population with metabolic syndrome and type-2 diabetes mellitus using shotgun metagenomic sequencing

Gut metagenome in pediatric subjects with metabolic syndrome (MetS) and type-2 diabetes mellitus (T2DM) has been poorly studied, despite an alarming worldwide increase in the prevalence and incidence of obesity and MetS within this population. The objective of this study was to characterize the gut microbiome taxonomic composition of Mexican pediatric subjects with MetS and T2DM using shotgun metagenomics and analyze the potential relationship with metabolic changes and proinflammatory effects. Paired-end reads of fecal DNA samples were obtained through the Illumina HiSeq X Platform. Statistical analyses and correlational studies were conducted using gut microbiome data and metadata from all individuals. Gut microbial dysbiosis was observed in MetS and T2DM children compared to healthy subjects, which was characterized by an increase in facultative anaerobes (i.e., enteric and lactic acid bacteria) and a decrease in strict anaerobes (i.e., Erysipelatoclostridium, Shaalia, and Actinomyces genera). This may cause a loss of gut hypoxic environment, increased gut microbial nitrogen metabolism, and higher production of pathogen-associated molecular patterns. These metabolic changes may trigger the activation of proinflammatory activity and impair the host's intermediate metabolism, leading to a possible progression of the characteristic risk factors of MetS and T2DM, such as insulin resistance, dyslipidemia, and an increased abdominal circumference. Furthermore, specific viruses (Jiaodavirus genus and Inoviridae family) showed positive correlations with proinflammatory cytokines involved in these metabolic diseases. This study provides novel evidence for the characterization of MetS and T2DM pediatric subjects in which the whole gut microbial composition has been characterized. Additionally, it describes specific gut microorganisms with functional changes that may influence the onset of relevant health risk factors

Perfil de sensibilización a alergenos en niños con dermatitis atópica atendidos en el Servicio de Alergología del Hospital Universitario de la Universidad Autónoma de Nuevo León, México

La sensibilización a alergenos observada en la dermatitis atópica aumenta el riesgo del niño a padecer rinitis alérgica y asma. Los estudios recientes indican que entre mayor actividad de proteasas haya en los alergenos a los que se está sensibilizado, hay mayor defecto en la barrera cutánea y mayor gravedad de la enfermedad. ABSTRACT Sensitization to allergens in atopic dermatitis patients is a risk factor for developing asthma and allergic rhinitis in the future, as well as an aggravating factor in the course of the disease. Recent studies have attributed the activity of the proteases of some antigens to cause a grater defect in the epithelial barrier and a more severe disease

Isoprenylcysteine Carboxylmethyltransferase-Based Therapy for Hutchinson-Gilford Progeria Syndrome.

Hutchinson-Gilford progeria syndrome (HGPS, progeria) is a rare genetic disease characterized by premature aging and death in childhood for which there were no approved drugs for its treatment until last November, when lonafarnib obtained long-sought FDA approval. However, the benefits of lonafarnib in patients are limited, highlighting the need for new therapeutic strategies. Here, we validate the enzyme isoprenylcysteine carboxylmethyltransferase (ICMT) as a new therapeutic target for progeria with the development of a new series of potent inhibitors of this enzyme that exhibit an excellent antiprogeroid profile. Among them, compound UCM-13207 significantly improved the main hallmarks of progeria. Specifically, treatment of fibroblasts from progeroid mice with UCM-13207 delocalized progerin from the nuclear membrane, diminished its total protein levels, resulting in decreased DNA damage, and increased cellular viability. Importantly, these effects were also observed in patient-derived cells. Using the Lmna G609G/G609G progeroid mouse model, UCM-13207 showed an excellent in vivo efficacy by increasing body weight, enhancing grip strength, extending lifespan by 20%, and decreasing tissue senescence in multiple organs. Furthermore, UCM-13207 treatment led to an improvement of key cardiovascular hallmarks such as reduced progerin levels in aortic and endocardial tissue and increased number of vascular smooth muscle cells (VSMCs). The beneficial effects go well beyond the effects induced by other therapeutic strategies previously reported in the field, thus supporting the use of UCM-13207 as a new treatment for progeria.This work was supported by grants from The Progeria Research Foundation (PRF 2016-65) and the Spanish MINECO (PID2019-106279RB-I00, PID2019-108489RBI00). The authors thank Fundación La Caixa (A.G.), CEI Moncloa (N.I.M.-R.), MINECO (F.J.O.-N. and M.B.) and Ministerio de Ciencia, Innovación y Universidades (N.K.-F.) for predoctoral fellowships. The authors thank C. López-Otín for kindly donating LmnaG609G/G609G progeroid and their corresponding wild-type fibroblasts and UCM’s CAIs Cytometry and Fluorescence Microscopy, Genomics, NMR, and Mass Spectrometry, for their assistance. The CNIC is supported by the Ministerio de Ciencia e Innovación, the Instituto de Salud Carlos III, and the pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant SEV-2015- 0505). The generation of the antiprogerin antibody was funded by the Wellcome Trust (098291/Z/12/Z to S.N.).S

Efectos de la reforestación en la sensibilización al polen de árboles en habitantes de Nuevo León, México

Las áreas verdes urbanas son importantes en la planeación de las ciudades para promover la interacción de los ciudadanos con el ambiente y la salud. La falta de planeación y diseño de estas áreas y la mala selección de árboles han contribuido a aumentar la incidencia de alergia al polen entre la población. Con frecuencia los programas de reforestación ambiental no toman en cuenta el potencial alergénico de algunas especies. El gobierno de Nuevo León en los últimos cuatro años ha plantado cerca de 18 mil árboles de la especie Quercus, además de un número indeterminado de árboles de la especie Fraxinus, cuyo polen es alergénico. Objetivos: identificar el cambio en la sensibilización al polen de árboles de acuerdo con los programas de reforestación ambiental. ABSTRACT Climate change has implications for health, ecology and society. Urban green areas are a key element in the planning of cities, promoting citizen interaction with the environment, as well as health. Lack of planning and design of these areas as well as the selection of ornamental trees can be a trigger of pollen allergy in the surrounding population. Reforestation is among the programs implemented by the government that have an impact on allergy. Environmental reforestation programs do not take into account the allergenic potential of some species. In the last 4 years, the government of Nuevo Leon, Mexico, has planted nearly 18,000 Quercus species trees, in addition to an unknown number of Fraxinus species trees that are listed as tree species with high pollen production. Objective: To identify changes in tree pollen sensitization, based on environmental reforestation programs

Novel Antagonist of the Type 2 Lysophosphatidic Acid Receptor (LPA2), UCM-14216, Ameliorates Spinal Cord Injury in Mice

Spinal cord injuries (SCIs) irreversibly disrupt spinal connectivity, leading to permanent neurological disabilities. Current medical treatments for reducing the secondary damage that follows the initial injury are limited to surgical decompression and anti-inflammatory drugs, so there is a pressing need for new therapeutic strategies. Inhibition of the type 2 lysophosphatidic acid receptor (LPA2) has recently emerged as a new potential pharmacological approach to decrease SCIassociated damage. Toward validating this receptor as a target in SCI, we have developed a new series of LPA2 antagonists, among which compound 54 (UCM14216) stands out as a potent and selective LPA2 receptor antagonist (Emax = 90%, IC50 = 1.9 μM, KD = 1.3 nM; inactive at LPA1,3−6 receptors). This compound shows efficacy in an in vivo mouse model of SCI in an LPA2-dependent manner, confirming the potential of LPA2 inhibition for providing a new alternative for treating SCI

A divisão sexual do trabalho comunitário: Migrantes peruanos, informalidade e reprodução da vida em Córdoba, Argentina

Este artículo se propone indagar acerca de los modos de organización del trabajo comunitario que involucra a hombres y mujeres migrantes que habitan barrios de relegación urbana de la ciudad de Córdoba (Argentina). En particular, y a partir de los aportes teóricos de la economía feminista y los resultados de un trabajo de campo cualitativo con población migrante peruana en Córdoba, reflexiona sobre la división y jerarquización de género presente en el trabajo comunitario. El argumento principal afirma que, en escenarios de creciente informalización de la vida cotidiana migrante, lo comunitario resulta ser un factor tanto de sostenimiento y consolidación de los espacios donde reside un amplio conjunto de migrantes regionales como de subsistencia barrial y familiar.This article inquires about the ways of organizing community work involving male and female migrants who inhabit urban relegation neighborhoods in the city of Córdoba (Argentina). In particular, and based on the theoretical contributions of feminist economics and the results of qualitative field work with the Peruvian migrant population in Córdoba, it reflects upon the division and hierarchical organization of gender roles in community work. The main argument is that, in contexts of increasing informalization of migrant daily life, the community turns out to be a factor for sustaining and consolidating the spaces where a large group of regional migrants resides as well as a factor of neighborhood and family subsistence.Este artigo se propõe a indagar sobre os modos de organização do trabalho comunitário que envolve homens e mulheres migrantes que habitam bairros de relegação urbana da cidade de Córdoba (Argentina). Em particular, e a partir das colaborações teóricas da economia feminista e dos resultados de um trabalho de campo qualitativo com população migrante peruana em Córdoba, reflete sobre a divisão e hierarquização de gênero presente no trabalho comunitário. O argumento principal afirma que, em cenários de crescente infodos espaços onde reside um amplo conjunto de migrantes regionais quanto de subsistência de bairro e familiar.Fil: Magliano, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones y Estudios sobre Cultura y Sociedad. Universidad Nacional de Córdoba. Centro de Investigaciones y Estudios sobre Cultura y Sociedad; Argentin

Post-Franco Theatre

In the multiple realms and layers that comprise the contemporary Spanish theatrical landscape, “crisis” would seem to be the word that most often lingers in the air, as though it were a common mantra, ready to roll off the tongue of so many theatre professionals with such enormous ease, and even enthusiasm, that one is prompted to wonder whether it might indeed be a miracle that the contemporary technological revolution – coupled with perpetual quandaries concerning public and private funding for the arts – had not by now brought an end to the evolution of the oldest of live arts, or, at the very least, an end to drama as we know it