Hereditary angioedema.Treatment of acute attacks in Argentina

En el mundo, el angioedema hereditario (HAE) afecta a 1 de cada 50 000 personas. Produceepisodios de angioedema cutáneo, abdominal y laríngeos que generan gran incapacidad. Lamortalidad por la enfermedad oscila entre 15 y 50%. Aunque en Argentina un concentrado plasmático de C1inhibidor (pdC1INH) ha estado aprobado y disponible por décadas para el tratamiento del ataque agudo, solo15 (26%) de 58 pacientes había recibido pdC1INH alguna vez hasta el año 2008, y solo 2(3.4%) lo usaban regularmente.Luego de la aprobación de los nuevos medicamentos para HAE, incluido el icatibant en Argentinay de la publicación de las guías terapéuticas, 42 (82%) de 51 pacientes del grupo original tienen pdC1INH paratratar el próximo ataque. Sin embargo, 16 (18%) de estos pacientes continúan sin acceso a la medicación yotros 15 (35.7%) acceden a través de otro enfermo en forma espuria. Solo 12 (28.6%) de los pacientes con elmedicamento puede auto tratarse en su domicilio. La mejora en el acceso a la medicación es importante perodebe extenderse a todos los afectados y facilitarse el auto-tratamientoIn the world, hereditary angioedema (HAE) affects 1every 50 000 persons. It is characterized by highly disabling and recurrent episodes of cutaneous, abdominal and laryngeal episodes of angioedema. Asphyxia related mortality ranges from 15 to 50%. In Argentina a plasma derived C1 inhibitor concentrate (pdC1INH) has been available for the treatment of acute attacks for many decades, however, only15 (26%) out of 58 patients had received pdC1INH at least once until 2008, and only2 (3.4%) had used it regularly. After worldwide approval of the new drugs for the treatment of acute HAE attacks, adding icatibant to pdC1INH in Argentina, and after publication of the therapeutic guide for the country, 42 (82%) out of 51 patients from the original group has pdC1INH available to treat their next attack. However, 16 (18%) patients continue without access to medication and other 15 (35.7%) obtain their therapy spuriously through some other affected relative in their environment. Only 12 (28.6%) patients of the group self-treated at home. Access to treatment has greatly improved, but needs to be extended to all patients and self-treatment at home should be encouraged.Fil: Malbrán, Alejandro. Asociación Argentina de Angioedema Hereditario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Malbran, Eloisa. Asociación Argentina de Angioedema Hereditario; ArgentinaFil: Menéndez, Alejandra. Asociación Argentina de Angioedema Hereditario; ArgentinaFil: Fernández Romero, Diego S.. Asociación Argentina de Angioedema Hereditario; Argentin

Adverse events in 1395 infusions with different intravenous gammaglobulin products

Los procesos de aislamiento y esterilización de la gammaglobulina endovenosa (IVIG) afectan las características del producto terminado y, por lo tanto, su tolerabilidad. Distintos productos tienen diferentes incidencias de reacciones adversas. Este trabajo cuantifica los eventos adversos (EA) inmediatos provocados por distintas preparaciones de IVIG. Analizamos 1395 infusiones en 28 pacientes, con una mediana de 32.5 por sujeto (rango 2-214), utilizando seis preparados distintos de IVIG, con una dosis total promedio de 40.3 ± 8.3 g. Analizamos retrospectivamente 1 031 infusiones y 364 prospectivamente. Los pacientes utilizaron una media de 2.68 ± 1.8 IVIG diferentes, con una mediana de 2 (rango 1-6) por persona. El número de marcas comerciales utilizadas se relacionó con el número de infusiones recibidas, r = 0.73. En 24 (2.3%) de 1031 infusiones analizadas en forma retrospectiva se registraron EA que afectaron a 11 de los 23 casos incluidos, con una media de 2.18 ± 1.08 EA por afectado. De 24 pacientes y de 364 infusiones prospectivas, en 14 pacientes y en 32 (7.2%) procedimientos se observaron EA. Veinticuatro (42.9%) de 56 EA fueron leves, 31 (55.5%) moderados y uno (1.8%) fue grave. La velocidad de infusión fue de 9.04 ± 4.6 g/h para las que presentaron EA vs. 10.6 ± 4.6 g/h para las que no (p = 0.31). La incidencia, la gravedad y la proporción de pacientes afectados con EA para cada marca comercial de IVIG fueron muy diferentes entre sí. Esta información debe ser tomada en cuenta en el momento de selección de la IVIG a utilizar.Fil: Malbran, Alejandro. Hospital Britanico. Serv. de Alergia E Inmunologia Clinica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Larrauri, Blas. Hospital Britanico. Serv. de Alergia E Inmunologia Clinica; ArgentinaFil: Juri, María Cecilia . Hospital Britanico. Serv. de Alergia E Inmunologia Clinica; ArgentinaFil: Fernández Romero, Diego S.. Hospital Britanico. Serv. de Alergia E Inmunologia Clinica; Argentin

Non-singular radiation cosmological models

In this paper we analyse the possibility of constructing singularity-free inhomogeneous cosmological models with a pure radiation field as matter content. It is shown that the conditions for regularity are very easy to implement and therefore there is a huge number of such spacetimes.Comment: 13 pages, LaTex, ws-mpla, to appear in Modern Physics Letters

Common variable immunodeficiency. Epidemiology and clinical manifestations in 69 patients.

La inmunodeficiencia común variable (IDCV) se caracteriza por una alteración en la producción de anticuerpos y una mayor susceptibilidad a infecciones por bacterias extracelulares capsuladas, principalmente del tracto respiratorio. Analizamos las características clínicas de 69 pacientes, evaluados en un período de 10 años en tres centros de la ciudad de Buenos Aires. Al inicio del estudio se encontraban en seguimiento 14 pacientes y al finalizar 60; la mayoría fueron derivados por infecciones o hipogammaglobulinemia, y casi la mitad con diagnóstico establecido de inmunodeficiencia. Sesenta y cinco (94.2%) pacientes presentaron infecciones por gérmenes capsulados, cuatro (6.1%) sepsis y dos tuberculosis. La edad promedio de comienzo de los síntomas infecciosos fue de 18.1 años, la edad promedio al momento del diagnóstico fue de 29.6 años y el retraso diagnóstico de 11.9 años. En 41 (59.4%) pacientes se registró el antecedente de diarreas recurrentes o crónicas. En 22 (31.9%) se diagnosticaron 13 enfermedades autoinmunes, siendo las más frecuentes las hematológicas y el hipotiroidismo. Ocho pacientes tuvieron linfoproliferación policlonal histológica, cuatro (5.8%) como enfermedad granulomatosa de hígado, laringe y piel, y cuatro como neumonía intersticial linfoidea (NIL). Diecinueve (27.5%) pacientes presentaron esplenomegalia y 23/57 (40.3%) imágenes sugestivas de procesos granulomatosos o linfocíticos en la TAC de tórax (incluidos los 4 con NIL). Tres (4.3%) pacientes desarrollaron linfoma B, cuatro (5.8%) adenocarcinoma de estómago y uno cáncer de mama. El estudio tuvo una mediana de seguimiento de 54 meses, rango 1-353 y durante el período del mismo murieron cuatro pacientes (5.8%).Common variable immunodeficiency (CVID) is characterized by an impaired antibody production and an increased susceptibility to recurrent infections of the respiratory tract, mainly by extracellular encapsulated bacteria. We analyzed the clinical characteristics of 69 patients evaluated over a period of 10 years at three centers in the city of Buenos Aires. At the onset of the study 14 patients were on follow up, and at its end the number of patients reached to 60. Most of them consulted for infection or hypogammaglobulinemia and nearly half had an established diagnosis of immunodeficiency. Sixty-five (94.2%) patients had infections by encapsulated bacteria, four (6.1%) sepsis and two tuberculosis. The average age of onset of infectious symptoms was 18.1 years; the average age at diagnosis was 29.6 years and the delay to diagnosis 11.9 years. Forty one (59.4%) patients reported a history of recurrent or chronic diarrhea. In 22 (31.9%) 13 autoimmune diseases were diagnosed, being the most frequent the hematological disorders and hypothyroidism. Eight patients had histological polyclonal lymphoproliferation, four (5.8%) with granulomatous disease affecting the liver, the larynx and/or the skin; and four as lymphoid interstitial pneumonitis (LIP). Nineteen (27.5%) patients had splenomegaly and 23/57 (40.3%) images suggestive of lymphocytic or granulomatous processes (including the 4 with LIP) in the chest CT. Three (4.3%) patients developed B cell lymphoma, four (5.8%) stomach adenocarcinoma and one breast cancer. The study had a median follow-up of 54 months, range 1-353 and four patients (5.8%) died during the follow up.Fil: Fernández Romero, Diego S.. Hospital Britanico. Serv. de Alergia E Inmunologia Clinica; ArgentinaFil: Juri, María C.. Hospital Britanico. Serv. de Alergia E Inmunologia Clinica; ArgentinaFil: Paolini, María V.. Hospital Durand; ArgentinaFil: Malbran, Alejandro. Hospital Britanico. Serv. de Alergia E Inmunologia Clinica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Crystallization and preliminary crystallographic studies of human kallikrein 7, a serine protease of the multigene kallikrein family

4 páginas, 6 figuras, 2 tablas -- PAGS nros. 669-672Hepatitis B core (HBc) particles have been extensively exploited as carriers for foreign immunological epitopes in the development of multicomponent vaccines and diagnostic reagents. Crystals of the T = 4 HBc particle were grown in PEG 20 000, ammonium sulfate and various types of alcohols. A temperature jump from 277 or 283 to 290 K was found to enhance crystal growth. A crystal grown using MPD as a cryoprotectant diffracted X-rays to 7.7 Å resolution and data were collected to 99.6% completeness at 8.9 Å. The crystal belongs to space group P212121, with unit-cell parameters a = 352.3, b = 465.5, c = 645.0 Å. The electron-density map reveals a protrusion that is consistent with the N-terminus extending out from the surface of the capsid. The structure presented here supports the idea that N-terminal insertions can be exploited in the development of diagnostic reagents, multicomponent vaccines and delivery vehicles into mammalian cellsWe thank Professor K. Murray for providing plasmid pR1-11E. X-ray data collection was supported by BM14UK/ESRF, Grenoble and SRS, Daresbury. WST was supported by a Die NorKen Stiftung Visiting Fellowship and KLH is the recipient of the Darwin Trust ScholarshipPeer reviewe

Episodic Vestibulocerebellar Ataxia Associated with a CACNA1G Missense Variant

Episodic vestibulocerebellar ataxias are rare diseases, frequently linked to mutations in different ion channels. Our objective in this work was to describe a kindred with episodic vestibular dysfunction and ataxia, associated with a novel CACNA1G variant. Two individuals from successive generations developed episodes of transient dizziness, gait unsteadiness, a sensation of fall triggered by head movements, headache, and cheek numbness. These were suppressed by carbamazepine (CBZ) administration in the proband, although acetazolamide and topiramate worsened instability, and amitriptyline and flunarizine did not prevent headache spells. On examination, the horizontal head impulse test (HIT) yielded saccadic responses bilaterally and was accompanied by cerebellar signs. Two additional family members were asymptomatic, with normal neurological examinations. Reduced vestibulo-ocular reflex gain values, overt and covert saccades were shown by video-assisted HIT in affected subjects. Hearing acuity was normal. Whole-exome sequencing demonstrated the heterozygous CACNA1G missense variant c.6958G>T (p.Gly2320Cys) in symptomatic individuals. It was absent in 1 unaffected member (not tested in the other asymptomatic individual) and should be considered likely pathogenic. CACNA1G encodes for the pore-forming, a1G subunit of the T-type voltage-gated calcium channel (VGCC), in which currents are transient owing to fast inactivation, and tiny, due to small conductance. Mutations in CACNA1G cause generalized absence epilepsy and adult-onset, dominantly inherited, spinocerebellar ataxia type 42. In this kindred, the aforementioned CACNA1G variant segregated with disease, which was consistent with episodic vestibulocerebellar ataxia. CBZ proved successful in bout prevention and provided symptomatic benefit in the proband, probably as a result of interaction of this drug with VGCC. Further studies are needed to fully determine the vestibular and neurological manifestations of this form of episodic vestibulocerebellar ataxia. This novel disease variant could be designated episodic vestibulocerebellar ataxia type 10. © 2021 The Author(s). Published by S. Karger AG, Basel

NIRS potential use for the determination of natural resources quality from dehesa (acorn and grass) in Montanera system for Iberian pigs.

NIRS technology has been used as an alternative to conventional methods to determinate the content of nutrients of acorns and grass from dehesa ecosystem. Dry matter (DM), crude fat (CF), crude protein (CP), starch, total phenolic compounds (TP), α-tocopherol, γ-tocopherol, fatty acids, neutral detergent fiber (NDF), total antioxidant activity (TAA) and total energy (TE) were determined by conventional methods for later development of NIRS predictive equations. The NIR spectrum of each sample was collected and for all studied parameters, a predictive model was obtained and external validated. Good prediction equations were obtained for moisture, crude fat, crude protein, total energy and γ-tocopherol in acorns samples, with high coefficients of correlation (1-VR) and low standard error of prediction (SEP) (1-VR=0.81, SEP=2.62; 1-VR=0.92, SEP=0.54; 1-VR=0.86, SEP=0.47; 1-VR=0.84, SEP=0.2; 1-VR=0.88, SEP=5.4, respectively) and crude protein, NDF, α-tocopherol and linolenic acid content in grass samples (1-VR=0.9, SEP=1.99; 1-VR=0.87, SEP=4.13; 1-VR=0.76, SEP=10.9; 1-VR=0.82, SEP=0.6, respectively). Therefore, these prediction models could be used to determinate the nutritional composition of Montanera natural resources

Location of Bioelectricity Plants in the Madrid Community Based on Triticale Crop: A Multicriteria Methodology

This paper presents a work whose objective is, first, to quantify the potential of the triticale biomass existing in each of the agricultural regions in the Madrid Community through a crop simulation model based on regression techniques and multiple correlation. Second, a methodology for defining which area has the best conditions for the installation of electricity plants from biomass has been described and applied. The study used a methodology based on compromise programming in a discrete multicriteria decision method (MDM) context. To make a ranking, the following criteria were taken into account: biomass potential, electric power infrastructure, road networks, protected spaces, and urban nuclei surfaces. The results indicate that, in the case of the Madrid Community, the Campiña region is the most suitable for setting up plants powered by biomass. A minimum of 17,339.9 tons of triticale will be needed to satisfy the requirements of a 2.2 MW power plant. The minimum range of action for obtaining the biomass necessary in Campiña region would be 6.6 km around the municipality of Algete, based on Geographic Information Systems. The total biomass which could be made available in considering this range in this region would be 18,430.68 t

Relativistically extended Blanchard recurrence relation for hydrogenic matrix elements

General recurrence relations for arbitrary non-diagonal, radial hydrogenic matrix elements are derived in Dirac relativistic quantum mechanics. Our approach is based on a generalization of the second hypervirial method previously employed in the non-relativistic Schr\"odinger case. A relativistic version of the Pasternack-Sternheimer relation is thence obtained in the diagonal (i.e. total angular momentum and parity the same) case, from such relation an expression for the relativistic virial theorem is deduced. To contribute to the utility of the relations, explicit expressions for the radial matrix elements of functions of the form $r^\lambda$ and $\beta r^\lambda$ ---where $\beta$ is a Dirac matrix--- are presented.Comment: 21 pages, to be published in J. Phys. B: At. Mol. Opt. Phys. in Apri

Validation of an Aesthetic Assessment System for Commercial Tasks

[Abstract] Automatic prediction of the aesthetic value of images has received increasing attention in recent years. This is due, on the one hand, to the potential impact that predicting the aesthetic value has on practical applications. Even so, it remains a difficult task given the subjectivity and complexity of the problem. An image aesthetics assessment system was developed in recent years by our research group. In this work, its potential to be applied in commercial tasks is tested. With this objective, a set of three portals and three real estate agencies in Spain were taken as case studies. Images of their websites were taken to build the experimental dataset and a validation method was developed to test their original order with another proposed one according to their aesthetic value. So, in this new order, the images that have the high aesthetic score by the AI system will occupy the first positions of the portal. Relevant results were obtained, with an average increase of 52.54% in the number of clicks on the ads, in the experiment with Real Estate portals. A statistical analysis prove that there is a significant difference in the number of clicks after selecting the images with the AI system.This work is supported by the General Directorate of Culture, Education and University Management of Xunta de Galicia (Ref. ED431D 201716), Competitive Reference Groups (Ref. ED431C 201849) and Ministry of Science and Innovation project Society challenges (Ref. PID2020-118362RB-I00). We also wish to acknowledge the support received from the Centro de Investigación de Galicia “CITIC”, funded by Xunta de Galicia and the European Union (European Regional Development Fund- Galicia 2014-2020 Program), by grant ED431G 2019/01Xunta de Galicia; ED431D 201716Xunta de Galicia; ED431C 201849Xunta de Galicia; ED431G 2019/0