Advances in primary immunodeficiency diseases in Latin America: epidemiology, research, and perspectives

Primary immunodeficiencies (PIDs) are genetic disorders of the immune system comprising many different phenotypes. Although previously considered rare, recent advances in their clinical, epidemiological, and molecular definitions are revealing how much we still need to learn about them. For example, geographical and ethnic variations as well as the impact of certain practices influence their frequency and presentation, making it necessary to consider their study in terms of regions. The Latin American Society for Immunodeficiencies was established as an organization dedicated to provide scientific support for basic and clinical research and to develop tools and educational resources to promote awareness in the medical community. Initiatives such as these are positively influencing the way PIDs are tackled in these countries, as shown by recent reports and publications. This paper provides a historical compilation and a current view of the many issues faced by scientists studying these diseases in these countries, highlighting the diverse scientific contributions and offering a promising perspective for the further developments in this field in Latin America

Failing to Make Ends Meet: The Broad Clinical Spectrum of DNA Ligase IV Deficiency. Case Series and Review of the Literature

DNA repair defects are inborn errors of immunity that result in increased apoptosis and oncogenesis. DNA Ligase 4-deficient patients suffer from a wide range of clinical manifestations since early in life, including: microcephaly, dysmorphic facial features, growth failure, developmental delay, mental retardation; hip dysplasia, and other skeletal malformations; as well as a severe combined immunodeficiency, radiosensitivity, and progressive bone marrow failure; or, they may present later in life with hematological neoplasias that respond catastrophically to chemo- and radiotherapy; or, they could be asymptomatic. We describe the clinical, laboratory, and genetic features of five Mexican patients with LIG4 deficiency, together with a review of 36 other patients available in PubMed Medline. Four out of five of our patients are dead from lymphoma or bone marrow failure, with severe infection and massive bleeding; the fifth patient is asymptomatic despite a persistent CD4+ lymphopenia. Most patients reported in the literature are microcephalic females with growth failure, sinopulmonary infections, hypogammaglobulinemia, very low B-cells, and radiosensitivity; while bone marrow failure and malignancy may develop at a later age. Dysmorphic facial features, congenital hip dysplasia, chronic liver disease, gradual pancytopenia, lymphoma or leukemia, thrombocytopenia, and gastrointestinal bleeding have been reported as well. Most mutations are compound heterozygous, and all of them are hypomorphic, with two common truncating mutations accounting for the majority of patients. Stem-cell transplantation after reduced intensity conditioning regimes may be curative

Vulnerabilidad territorial ante la expansión urbana

En México según el INEGI para el 2010 la población urbana fue del 77.8%, lo que significa que un porcentaje importante de la población vive en localidades mayores a los 2500 habitantes. Las cuales tienen sus propios ritmos de crecimiento, funciones, especialización, cambios de usos del suelo y problemáticas específicas. Las ciudades principales se han expandido, en las últimas décadas, con escasa acción planificadora y bajos resultados en el ordenamiento territorial. Ello ha configurado crecimientos físicos dispersos y fragmentados con importantes efectos ambientales. En México, la dispersión urbana genera ocupación del territorio en riesgos, situaciones de vulnerabilidad con inexistencia de acciones públicas, porque se encuentra en pendientes abruptas, lugares que se inundan, en áreas naturales protegidas, entre otras formas, genera tejido construido en áreas no óptimas para el desarrollo urbano, todo ello impacta negativamente al medio ambiente y la calidad de vida de la población. El crecimiento urbano continuará porque en las ciudades se genera la riqueza del país, en ellas se encuentran las oportunidades y soluciones. La urbanización es el modelo para conseguir el desarrollo de la sociedad. En dicho desarrollo se aspira el crecimiento sustentable y armonioso con el ambiente. Se espera cambios regulatorios para revertir los efectos negativos generados durante décadas con la expansión urbana consumidora de recursos naturales, energía y recursos financieros. En este marco problemático se integra el libro “Vulnerabilidad territorial ante la expansión urbana”, es producto de las actividades científicas –foro y congreso realizados en 2015- de la Red internacional de territorios, sustentabilidad y gobernanza en México y Polonia (RETESYG) de la Facultad de Geografía, Facultad de Planeación Urbana y Regional de la Universidad Autónoma del Estado de México (UAEM), así como de la Facultad de Geografía y Estudios Regionales de la Universidad de Varsovia (UV) y la Facultad de Geografía y Biología de la Universidad Pedagógica “Comisión de Educación Nacional” de Cracovia. El libro tiene una visión integral de la vulnerabilidad territorial ante la expansión urbana, considera los enfoques de la geografía, de la planeación y del ordenamiento territorial para abordar las problemáticas ambiental y social. Presenta una visión amplia y de síntesis sobre vulnerabilidad del territorio y de las ciudades, en él se integran los saberes de la Geografía y de la Planeación Territorial. Destaca la necesidad de controlar el crecimiento anárquico y desordenado, las desigualdades sociales, los riesgos, los problemas ambientales, la falta de bases de datos geoespaciales dinámicas, entre otros. Los resultados de las investigaciones apuntan hacia el desarrollo territorial sustentable. El libro se conforma de dos partes, la primera presenta aspectos teóricos conceptuales y metodológicos de la vulnerabilidad territorial, estructural, física, ambiental y socioeconómica, los riesgos geomorfológicos, la sustentabilidad y manejo de recursos naturales, áreas naturales protegidas, metodologías para la evaluación de los impactos de la expansión metropolitana y gobernanza territorial. La segunda parte, desarrolla estudios de caso, a distintas escalas: desde huertos familiares, subcuentas, ciudad, municipio, zonas metropolitanas, megalópolis, regiones y país. En cada capítulo del libro se presenta bibliografía extensa, diversificada y actualizada que aportan al lector sobre el estado del arte de la vulnerabilidad territorial

Bullous lesions as a manifestation of systemic lupus erythematosus in two Mexican teenagers

Rarely, systemic lupus erythematosus (SLE) presents with bullous lesions due to severe edema and hydropic degeneration of the basal layer, or as a subepidermal blistering disease. Here, we describe two Mexican teenagers, one with SLE with blisters and another with bullous SLE. We also discuss the mechanisms and clinical implications of lesion formation in patients with SLE and bullae

A Generic Deep Learning Based Cough Analysis System from Clinically Validated Samples for Point-of-Need Covid-19 Test and Severity Levels

We seek to evaluate the detection performance of a rapid primary screening tool of Covid-19 solely based on the cough sound from 8,380 clinically validated samples with laboratory molecular-test (2,339 Covid-19 positive and 6,041 Covid-19 negative). Samples were clinically labelled according to the results and severity based on quantitative RT-PCR (qRT-PCR) analysis, cycle threshold and lymphocytes count from the patients. Our proposed generic method is a algorithm based on Empirical Mode Decomposition (EMD) with subsequent classification based on a tensor of audio features and deep artificial neural network classifier with convolutional layers called DeepCough'. Two different versions of DeepCough based on the number of tensor dimensions, i.e. DeepCough2D and DeepCough3D, have been investigated. These methods have been deployed in a multi-platform proof-of-concept Web App CoughDetect to administer this test anonymously. Covid-19 recognition results rates achieved a promising AUC (Area Under Curve) of 98.800.83%, sensitivity of 96.431.85%, and specificity of 96.201.74%, and 81.08%5.05% AUC for the recognition of three severity levels. Our proposed web tool and underpinning algorithm for the robust, fast, point-of-need identification of Covid-19 facilitates the rapid detection of the infection. We believe that it has the potential to significantly hamper the Covid-19 pandemic across the world

Heterozygous and Homozygous Variants in SORL1 Gene in Alzheimer's Disease Patients: Clinical, Neuroimaging and Neuropathological Findings

In the last few years, the SORL1 gene has been strongly implicated in the development of Alzheimer’s disease (AD). We performed whole-exome sequencing on 37 patients with early-onset dementia or family history suggestive of autosomal dominant dementia. Data analysis was based on a custom panel that included 46 genes related to AD and dementia. SORL1 variants were present in a high proportion of patients with candidate variants (15%, 3/20). We expand the clinical manifestations associated with the SORL1 gene by reporting detailed clinical and neuroimaging findings of six unrelated patients with AD and SORL1 mutations. We also present for the first time a patient with the homozygous truncating variant c.364C>T (p.R122*) in SORL1, who also had severe cerebral amyloid angiopathy. Furthermore, we report neuropathological findings and immunochemistry assays from one patient with the splicing variant c.4519+5G>A in the SORL1 gene, in which AD was confirmed by neuropathological examination. Our results highlight the heterogeneity of clinical presentation and familial dementia background of SORL1-associated AD and suggest that SORL1 might be contributing to AD development as a risk factor gene rather than as a major autosomal dominant gene.This work was supported by the Instituto de Salud Carlos III (PI17/01067) and AGAUR from the Autonomous Catalan Government (2017SGR1134). Dr. Víctor Antonio Blanco-Palmero is supported by the Instituto de Salud Carlos III (ISCIII, Spanish Biomedical Research Institute) through a “Río Hortega” contract (CM18/0095). Dr. Sara Llamas-Velasco is supported by the Instituto de Salud Carlos III (ISCIII; Spanish Biomedical Research Institute) through a “Juan Rodés” contract (JR 18/00046).S

Controlo químico de infestantes

Uma planta é considerada infestante quando nasce espontaneamente num local e momento indesejados, podendo interferir negativamente com a cultura instalada. As infestantes competem com as culturas para o espaço, a luz, água e nutrientes, podendo atrasar e prejudicar as operações de colheita, depreciar o produto final e assegurarem a reinfestação nas culturas seguintes. Dado o modo de propagação diferenciado das diversas espécies de infestantes, com as anuais a propagarem-se por semente e as perenes ou vivazes a assegurarem a sua propagação através de órgãos vegetativos (rizomas, bolbos, tubérculos, etc.), assim, também o seu controlo quer químico, quer mecânico terá que ser diferenciado, ou seja, para controlar infestantes anuais será suficiente destruir a sua parte aérea, enquanto para controlar infestantes perenes teremos que destruir os seus órgãos reprodutivos. O controlo de infestantes poderá ser químico, através da utilização de herbicidas, ou mecânico pela utilização de alfaias agrícolas, tais como a charrua de aivecas, a charrua de discos, a grade de discos, o escarificador e a fresa. Quando a técnica utilizada na instalação das culturas é a sementeira directa, o controlo das infestantes terá que ser obrigatoriamente químico, enquanto se o recurso à mobilização do solo for a técnica mais utilizada (sistema de mobilização tradicional ou sistema de mobilização reduzida), o controlo das infestantes tanto poderá ser químico como mecânico. Neste trabalho iremos abordar apenas, o controlo químico de infestantes

Attending to warning signs of primary immunodeficiencies disease across the range of clinical practices

Purpose: Patients with primary immunodeficiency diseases (PIDD) may present with recurrent infections affecting different organs, organ-specific inflammation/autoimmunity, and also increased cancer risk, particularly hematopoietic malignancies. The diversity of PIDD and the wide age range over which these clinical occurrences become apparent often make the identification of patients difficult for physicians other than immunologists. The aim of this report is to develop a tool for educative programs targeted to specialists and applied by clinical immunologists. Methods: Considering the data from national surveys and clinical reports of experiences with specific PIDD patients, an evidence-based list of symptoms, signs, and corresponding laboratory tests were elaborated to help physicians other than immunologists look for PIDD. Results: Tables including main clinical manifestations, restricted immunological evaluation, and possible related diagnosis were organized for general practitioners and 5 specialties. Tables include information on specific warning signs of PIDD for pulmonologists, gastroenterologists, dermatologists, hematologists, and infectious disease specialists. Conclusions: This report provides clinical immunologists with an instrument they can use to introduce specialists in other areas of medicine to the warning signs of PIDD and increase early diagnosis. Educational programs should be developed attending the needs of each specialty.Fil: Costa Carvalho, Beatriz Tavares. Universidade Federal de São Paulo; BrasilFil: Sevciovic Grumach, Anete. Fundação ABC. Faculdade de Medicina; BrasilFil: Franco, José Luis. Universidad de Antioquia; ColombiaFil: Espinosa Rosales, Francisco Javier. Instituto Nacional de Pediatría. Unidad de Investigación en Inmunodeficiencias; MéxicoFil: Leiva, Lily E.. State University of Louisiana; Estados UnidosFil: King, Alejandra. Hospital de Niños Doctor Luis Calvo Mackenna. Unidad de Inmunología; ChileFil: Porras, Oscar. Hospital Nacional de Niños “Dr. Carlos Sáenz Herrera”; Costa RicaFil: Bezrodnik, Liliana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Oleastro, Mathias. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Sorensen, Ricardo U.. State University of Louisiana; Estados Unidos. Universidad de La Frontera. Facultad de Medicina; MéxicoFil: Condino Neto, Antonio. Universidade de Sao Paulo; Brasi

Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis

Chronic mucocutaneous candidiasis disease (CMCD) may be caused by autosomal dominant (AD) IL-17F deficiency or autosomal recessive (AR) IL-17RA deficiency. Here, using whole-exome sequencing, we identified heterozygous germline mutations in STAT1 in 47 patients from 20 kindreds with AD CMCD. Previously described heterozygous STAT1 mutant alleles are loss-of-function and cause AD predisposition to mycobacterial disease caused by impaired STAT1-dependent cellular responses to IFN-γ. Other loss-of-function STAT1 alleles cause AR predisposition to intracellular bacterial and viral diseases, caused by impaired STAT1-dependent responses to IFN-α/β, IFN-γ, IFN-λ, and IL-27. In contrast, the 12 AD CMCD-inducing STAT1 mutant alleles described here are gain-of-function and increase STAT1-dependent cellular responses to these cytokines, and to cytokines that predominantly activate STAT3, such as IL-6 and IL-21. All of these mutations affect the coiled-coil domain and impair the nuclear dephosphorylation of activated STAT1, accounting for their gain-of-function and dominance. Stronger cellular responses to the STAT1-dependent IL-17 inhibitors IFN-α/β, IFN-γ, and IL-27, and stronger STAT1 activation in response to the STAT3-dependent IL-17 inducers IL-6 and IL-21, hinder the development of T cells producing IL-17A, IL-17F, and IL-22. Gain-of-function STAT1 alleles therefore cause AD CMCD by impairing IL-17 immunity