Browsing by Author "López, Javier"
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Item Cáncer de tráquea, bronquios y pulmón: análisis descriptivo de la situación epidemiológica en Chile(2022) López, Javier; Pettersen, María; Martinez, María; Bravo, Bárbara; Silva, María; Alliende, Martín; Arrau, CatalinaIntroducción: El Cáncer Pulmonar es el segundo cáncer más diagnosticado internacionalmente y posee la más alta tasa de mortalidad. Su principal factor de riesgo es el tabaquismo y destaca por tener manifestaciones clínicas tardías dificultando un diagnóstico precoz. Objetivo: Describir la situación epidemiológica del CP en Chile en cuanto a magnitud, tiempo, lugar y persona de las tasas de mortalidad. Metodología: Se realizó un análisis descriptivo cuantitativo de mortalidad en Chile a partir de registros del Departamento de Estadística e Información de Salud (DEIS) del Ministerio de Salud de Chile (MINSAL), entre los años 2002 y 2019. Resultado: Entre los años 2002-2019, las muertes por CP en Chile corresponden al 3.05% de las muertes totales y un 11,6% del total de muertes por neoplasias. Las tasas anuales de mortalidad ajustadas por edad muestran una disminución del 19,76% en hombres y un aumento del 13,6% en mujeres. La mayor y menor tasa ajustada de mortalidad promedio entre 2015-2019 la presenta la Región de Antofagasta y del Ñuble respectivamente. Discusión: En Chile la mortalidad por CP es más baja en relación al resto del mundo, sin embargo, es la primera causa de muerte por cáncer en hombres y tercera en mujeres. La mortalidad ajustada es mayor en la región de Antofagasta y en las mujeres se observa una mortalidad en aumento. Conclusión: Es importante identificar intervenciones de salud pública a nivel nacional como internacional que sean útiles para un tamizaje precoz de esta patología.Item Canine seroprevalence to Orientia species in southern Chile: A cross-sectional survey on the Chiloé Island(2018) Weitzel, Thomas; Jiang, Ju; Acosta-Jamett, Gerardo; Martínez-Valdebenito, Constanza; López, Javier; Richards, Allen L.; Abarca, KatiaBackground Scrub typhus is a potentially life-threatening vector-borne infection caused by Orientia species. It occurs mainly in the Asian-Pacific region, where it causes significant morbidity and mortality. Recently, an endemic focus of scrub typhus has been described in South America, on Chiloé Island in southern Chile. Dogs have been used as sentinel hosts to determine the presence and spatial distribution of various vector-borne infections. Their suitability to gain insight into human exposure to Orientia tsutsugamushi has been suggested in studies from Asia. Methodology In January 2016, we conducted a cross-sectional study, which included the two main cities on Chiloé Island. Canine blood samples were obtained in households, chosen by double stratified random sampling in urban and by convenience in rural locations. Specimens were tested by ELISA for IgG antibodies against whole-cell antigen preparations from three strains of O. tsutsugamushi. Data were further analyzed for factors associated with seropositivity including spatial clustering. Results Serum samples from 202 dogs (104 urban, 98 rural) were tested for IgG against O. tsutsugamushi, of which 43 (21.3%) were positive. Seroprevalence rates were higher in rural than in urban settings (p<0.01) and in older compared to younger dogs (p<0.01). Spatial analysis by LISA indicated the presence of four localities of highly grouped cases. Conclusions The detected seroprevalence supports the endemicity of scrub typhus in southern Chile and suggests a wide exposure of household dogs to the infected, yet unknown vector(s). The spatial data will be used for future research identifying further human cases as well as the local vector(s)/reservoirs for scrub typhus in southern Chile. The study reinforces that dogs are useful sentinels for Orientia spp. in regions of uncertain endemicity and distribution.Publication Data-driven historical characterization of epilepsy-associated genes(2022) Macnee, Marie; Pérez, Eduardo; López, Javier; Ivaniuk, Alina; May, Patrick; Møller, Rikke; Lal, DennisMany epilepsy-associated genes have been identified over the last three decades, revealing a remarkable molecular heterogeneity with the shared outcome of recurrent seizures. Information about the genetic landscape of epilepsies is scattered throughout the literature and answering the simple question of how many genes are associated with epilepsy is not straightforward. Here, we present a computationally driven analytical review of epilepsy-associated genes using the complete scientific literature in PubMed. Based on our search criteria, we identified a total of 738 epilepsy-associated genes. We further classified these genes into two Tiers. A broad gene list of 738 epilepsy-associated genes (Tier 2) and a narrow gene list composed of 143 epilepsy-associated genes (Tier 1). Our search criteria do not reflect the degree of association. The average yearly number of identified epilepsy-associated genes between 1992 and 2021 was 4.8. However, most of these genes were only identified in the last decade (2010-2019). Ion channels represent the largest class of epilepsy-associated genes. For many of these, both gain- and loss-of-function effects have been associated with epilepsy in recent years. We identify 28 genes frequently reported with heterogenous variant effects which should be considered for variant interpretation. Overall, our study provides an updated and manually curated list of epilepsy-related genes together with additional annotations and classifications reflecting the current genetic landscape of epilepsy.Item Geographical distribution and phylogenetic analysis of Rhipicephalus sanguineus sensu lato in northern and central Chile(2018) E. Díaz, Fabián; Martínez-Valdebenito, Constanza; López, Javier; Weitzel, Thomas; Abarca, KatiaThe presented study analyzed the presence and geographical distribution of the tropical and temperate lineages of Rhipicephalus sanguineus sensu lato in Chile. R. sanguineus s.l. ticks were collected from dogs at 14 sites in northern and central Chile for morphological and genetic analysis based on the 16S rDNA gene. Phylogenetic studies proved the existence of both, the tropical and the temperate lineages. The former was represented by a single haplotype and occurred in the far north; the latter included four haplotypes and was observed from the Tarapacá Region southwards. In four sites at latitudes from 20°S to 22°S, both lineages were found to coexist. Our study discovered for the first time the existence of the tropical lineage in Chile and demonstrated that distributions of the tropical and temperate lineages overlap, forming a transitional zone of approximately 200 km in northern coastal Chile.Item Prevalence and Risk Factors of Antibodies to Anaplasma spp. in Chile: A Household-Based Cross-Sectional Study in Healthy Adults and Domestic Dogs(2020) Acosta-Jamett, Gerardo; Weitzel, Thomas; López, Javier; Alvarado, Doris; Abarca, KatiaBackground: Pet-related tick-borne infections constitute an emerging problem in human and veterinary medicine worldwide. In Chile, two pathogens of the Anaplasmataceae family, Anaplasma platys and Ehrlichia canis, have been identified in recent years in dogs and vectors. This epidemiological survey aimed to determine the human and canine seroprevalence of Anaplasma spp. in urban and rural areas of different regions in Chile and to analyze the factors associated with seropositivity. Methods: We performed a cross-sectional household-based study in four regions, where healthy adults and their household dogs were included. Households were chosen by double stratified random sampling in urban areas and by convenience sampling in rural areas. Anaplasma seroreactivity was determined by a commercial microimmunofluorescence assay using Anaplasma phagocytophilum antigens. A questionnaire survey was applied to assess risk factors for Anaplasma seropositivity. Results: A total of 1105 persons and 905 dogs were included. The overall seroprevalence in humans was 9.4%, ranging from 5.6% in central Chile to 13.7% in the extreme north; in dogs the overall prevalence was 44.0% and ranged from 37.2% in the northern region to 61.1% in central Chile. Risk factors for human seropositivity were lower education and external deworming of dogs, whereas canine seropositivity was associated to urban site, mixed-breed, older animals, and tick infestation. Conclusions: This cross-sectional study suggests a broad exposure of both dogs and dog owners to Anaplasma or related agents in Chile. Further epidemiological and clinical studies are necessary to understand the complete spectrum and epidemiology of tick-borne zoonotic infections in the different ecoclimatic regions of Chile.Publication The genomic landscape across 474 surgically accessible epileptogenic human brain lesions(2022) López, Javier; Leu, Costin; Macnee, Marie; Khoury, Jean; Hoffmann, Lucas; Coras, Roland; Kobow, Katja; Bhattarai, Nisha; Pérez, Eduardo; Hamer, Hajo; Brandner, Sebastian; Rössler, Karl; Bien, Christian; Kalbhenn, Thilo; Pieper, Tom; Hartlieb, Till; Butler, Elizabeth; Genovese, Giulio; Becker, Kerstin; Altmüller, Janine; Niestroj, Lisa; Ferguson, Lisa; Busch, Robyn; Nürnberg, Peter; Najm, Imad; Blümcke, Ingmar; Lal, DennisUnderstanding the exact molecular mechanisms involved in the etiology of epileptogenic pathologies with or without tumor activity is essential for improving treatment of drug-resistant focal epilepsy. Here, we characterize the landscape of somatic genetic variants in resected brain specimens from 474 individuals with drug-resistant focal epilepsy using deep whole-exome sequencing (>350×) and whole-genome genotyping. Across the exome, we observe a greater number of somatic single-nucleotide variants (SNV) in low-grade epilepsy-associated tumors (LEAT; 7.92 ± 5.65 SNV) than in brain tissue from malformations of cortical development (MCD; 6.11 ± 4 SNV) or hippocampal sclerosis (HS; 5.1 ± 3.04 SNV). Tumor tissues also had the largest number of likely pathogenic variant carrying cells. LEAT had the highest proportion of samples with one or more somatic copy number variants (CNV; 24.7%), followed by MCD (5.4%) and HS (4.1%). Recurring somatic whole chromosome duplications affecting Chromosome 7 (16.8%), chromosome 5 (10.9%), and chromosome 20 (9.9%) were observed among LEAT. For germline variant-associated MCD genes such as TSC2, DEPDC5, and PTEN, germline SNV were frequently identified within large loss of heterozygosity regions, supporting the recently proposed 'second hit' disease mechanism in these genes. We detect somatic variants in twelve established lesional epilepsy genes and demonstrate exome-wide statistical support for three of these in the etiology of LEAT (e.g., BRAF) and MCD (e.g., SLC35A2 and MTOR). We also identify novel significant associations for PTPN11 with LEAT and NRAS Q61 mutated protein with a complex MCD characterized by polymicrogyria and nodular heterotopia. The variants identified in NRAS are known from cancer studies to lead to hyperactivation of NRAS, which can be targeted pharmacologically. We identify large recurrent 1q21-q44 duplication including AKT3 in association with focal cortical dysplasia type 2a with hyaline astrocytic inclusions, another rare and possibly under-recognized brain lesion. The clinical genetic analyses showed that the numbers of somatic SNV across the exome and the fraction of affected cells were positively correlated with the age at seizure onset and surgery in individuals with LEAT. In summary, our comprehensive genetic screen sheds light on the genome-scale landscape of genetic variants in epileptic brain lesions, informs the design of gene panels for clinical diagnostic screening, and guides future directions for clinical implementation of epilepsy surgery genetics.