Surveillance of Salmonella enterica serovar Typhi in Colombia, 2012-2015.

Salmonella Typhi (S. Typhi) is the causative agent of typhoid fever; a systemic disease affecting ~20 million people per year globally. There are little data regarding the contemporary epidemiology of typhoid in Latin America. Consequently, we aimed to describe some recent epidemiological aspects of typhoid in Colombia using cases reported to the National Public Health Surveillance System (Sivigila) between 2012 and 2015. Over the four-year reporting period there were 836 culture confirmed cases of typhoid in Colombia, with the majority (676/836; 80.1%) of reported cases originated from only seven departments. We further characterized 402 S. Typhi isolates with available corresponding data recovered from various departments of Colombia through antimicrobial susceptibility testing and molecular subtyping. The majority (235/402; 58.5%) of these typhoid cases occurred in males and were most commonly reported in those aged between 10 and 29 years (218/402; 54.2%); there were three (0.74%) reported fatalities. The overwhelming preponderance (339/402; 84.3%) of S. Typhi were susceptible to all tested antimicrobials. The most common antimicrobial to which the organisms exhibited non-susceptibility was ampicillin (30/402;7.5%), followed by nalidixic acid (23/402, 5.7%). Molecular subtyping identified substantial genetic diversity, which was well distributed across the country. Despite the diffuse pattern of S. Typhi genotypes, we identified various geographical hotspots of disease associated with local dominant genotypes. Notably, we found limited overlap of Colombian genotypes with organisms reported in other Latin American countries. Our work highlights a substantial burden of typhoid in Colombia, characterized by sustained transmission in some regions and limited epidemics in other departments. The disease is widely distributed across the country and associated with multiple antimicrobial susceptible genotypes that appear to be restricted to Colombia. This study provides a current perspective for typhoid in Latin America and highlights the importance of pathogen-specific surveillance to add insight into the limited epidemiology of typhoid in this region

Multi-Determinants Analysis of Molecular Alterations for Predicting Clinical Benefit to EGFR-Targeted Monoclonal Antibodies in Colorectal Cancer

KRAS mutations occur in 35-45% of metastatic colorectal cancers (mCRC) and preclude responsiveness to EGFR-targeted therapy with cetuximab or panitumumab. However, less than 20% patients displaying wild-type KRAS tumors achieve objective response. Alterations in other effectors downstream of the EGFR, such as BRAF, and deregulation of the PIK3CA/PTEN pathway have independently been found to give rise to resistance. We present a comprehensive analysis of KRAS, BRAF, PIK3CA mutations, and PTEN expression in mCRC patients treated with cetuximab or panitumumab, with the aim of clarifying the relative contribution of these molecular alterations to resistance.We retrospectively analyzed objective tumor response, progression-free (PFS) and overall survival (OS) together with the mutational status of KRAS, BRAF, PIK3CA and expression of PTEN in 132 tumors from cetuximab or panitumumab treated mCRC patients. Among the 106 non-responsive patients, 74 (70%) had tumors with at least one molecular alteration in the four markers. The probability of response was 51% (22/43) among patients with no alterations, 4% (2/47) among patients with 1 alteration, and 0% (0/24) for patients with > or =2 alterations (p<0.0001). Accordingly, PFS and OS were increasingly worse for patients with tumors harboring none, 1, or > or =2 molecular alteration(s) (p<0.001).When expression of PTEN and mutations of KRAS, BRAF and PIK3CA are concomitantly ascertained, up to 70% of mCRC patients unlikely to respond to anti-EGFR therapies can be identified. We propose to define as 'quadruple negative', the CRCs lacking alterations in KRAS, BRAF, PTEN and PIK3CA. Comprehensive molecular dissection of the EGFR signaling pathways should be considered to select mCRC patients for cetuximab- or panitumumab-based therapies

Genomics of the Argentinian cholera epidemic elucidate the contrasting dynamics of epidemic and endemic Vibrio cholerae

Funder: U.S. Department of Health & Human Services | National Institutes of Health (NIH)Abstract: In order to control and eradicate epidemic cholera, we need to understand how epidemics begin, how they spread, and how they decline and eventually end. This requires extensive sampling of epidemic disease over time, alongside the background of endemic disease that may exist concurrently with the epidemic. The unique circumstances surrounding the Argentinian cholera epidemic of 1992–1998 presented an opportunity to do this. Here, we use 490 Argentinian V. cholerae genome sequences to characterise the variation within, and between, epidemic and endemic V. cholerae. We show that, during the 1992–1998 cholera epidemic, the invariant epidemic clone co-existed alongside highly diverse members of the Vibrio cholerae species in Argentina, and we contrast the clonality of epidemic V. cholerae with the background diversity of local endemic bacteria. Our findings refine and add nuance to our genomic definitions of epidemic and endemic cholera, and are of direct relevance to controlling current and future cholera epidemics

Digitale Lehr-, Lern- und Forschungsressourcen für die deutsche Sprache: Theorie und Empirie

Dieser Band ist den digitalen Offline- und Online-Ressourcen für das Lehren, Lernen und Forschen im Bereich der deutschen Sprache und der deutschen Sprachwissenschaft gewidmet. Er richtet sich in erster Linie an Sprachwissenschaftler und an Universitätsdozenten, aber auch an alle potenziellen Wissenschaftler und Nutzer, die sich für die deutsche Sprache und die deutsche Sprachwissenschaft interessieren und von den hier präsentierten digitalen Ressourcen profitieren können

Genotypic diversity of Salmonella ser. Abortusequi isolates from Argentina

Fil: Bustos, C. P. Instituto Nacional de Tecnología Agropecuaria. Centro Nacional de Investigaciones Agropecuarias. Instituto de Patobiología; Argentina.Fil: Moroni, M. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Bacteriología. Servicio de Enterobacterias; Argentina.Fil: Caffer, María Ines. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Bacteriología. Servicio de Enterobacterias; Argentina.Fil: Ivanissevich, A. Cresal Veterinaria; Argentina.Fil: Herrera, M. Servicio Nacional de Sanidad y Calidad Agropecuaria (SENASA). DiLab, Departamento de Salmonelosis; Argentina.Fil: Moreira, A. R. Instituto Nacional de Tecnología Agropecuaria. Estación Experimental Agropecuaria Balcarse; Argentina.Fil: Guida, Nora. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Cátedra de Enfermedades Infecciosas; Argentina.Fil: Chacana, Pablo. Instituto Nacional de Tecnología Agropecuaria. Centro Nacional de Investigaciones Agropecuarias. Instituto de Patobiología; Argentina.Salmonella enterica subsp. enterica serovar Abortusequi (S. Abortusequi) is a serotype restricted to equines, which produces abortion outbreaks. Nowadays the disease is being reported in different countries including Argentina thus generating an important impact in the equine industry. Molecular characterization of the 95 kb virulence plasmid and the spvC gene of S. Abortusequi demonstrated their importance in the pathogenicity of the serotype. In the last decades, high clonality of S. Abortusequi was identified in Japan, Mongolia and Croatia

Genotypic diversity of Salmonella

Fil: Bustos, C. P. Instituto Nacional de Tecnología Agropecuaria. Centro Nacional de Investigaciones Agropecuarias. Instituto de Patobiología; Argentina.Fil: Moroni, M. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Bacteriología. Servicio de Enterobacterias; Argentina.Fil: Caffer, María Ines. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Bacteriología. Servicio de Enterobacterias; Argentina.Fil: Ivanissevich, A. Cresal Veterinaria; Argentina.Fil: Herrera, M. Servicio Nacional de Sanidad y Calidad Agropecuaria (SENASA). DiLab, Departamento de Salmonelosis; Argentina.Fil: Moreira, A. R. Instituto Nacional de Tecnología Agropecuaria. Estación Experimental Agropecuaria Balcarse; Argentina.Fil: Guida, Nora. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Cátedra de Enfermedades Infecciosas; Argentina.Fil: Chacana, Pablo. Instituto Nacional de Tecnología Agropecuaria. Centro Nacional de Investigaciones Agropecuarias. Instituto de Patobiología; Argentina.Salmonella enterica subsp. enterica serovar Abortusequi (S. Abortusequi) is a serotype restricted to equines, which produces abortion outbreaks. Nowadays the disease is being reported in different countries including Argentina thus generating an important impact in the equine industry. Molecular characterization of the 95 kb virulence plasmid and the spvC gene of S. Abortusequi demonstrated their importance in the pathogenicity of the serotype. In the last decades, high clonality of S. Abortusequi was identified in Japan, Mongolia and Croatia

Genomics of the Argentinian cholera epidemic elucidate the contrasting dynamics of epidemic and endemic Vibrio cholerae

Funder: U.S. Department of Health & Human Services | National Institutes of Health (NIH)Abstract: In order to control and eradicate epidemic cholera, we need to understand how epidemics begin, how they spread, and how they decline and eventually end. This requires extensive sampling of epidemic disease over time, alongside the background of endemic disease that may exist concurrently with the epidemic. The unique circumstances surrounding the Argentinian cholera epidemic of 1992–1998 presented an opportunity to do this. Here, we use 490 Argentinian V. cholerae genome sequences to characterise the variation within, and between, epidemic and endemic V. cholerae. We show that, during the 1992–1998 cholera epidemic, the invariant epidemic clone co-existed alongside highly diverse members of the Vibrio cholerae species in Argentina, and we contrast the clonality of epidemic V. cholerae with the background diversity of local endemic bacteria. Our findings refine and add nuance to our genomic definitions of epidemic and endemic cholera, and are of direct relevance to controlling current and future cholera epidemics

Supporting data for "Genomics of the Argentinian cholera epidemic elucidate the contrasting dynamics of epidemic and endemic Vibrio cholerae"

In order to control and eradicate epidemic cholera, we need to understand how epidemics begin, how they spread, and how they decline and eventually end. This requires extensive sampling of epidemic disease over time, alongside the background of endemic disease that may exist concurrently with the epidemic. The unique circumstances surrounding the Argentinian cholera epidemic of 1992–1998 presented an opportunity to do this. Here, we use 490 Argentinian V. cholerae genome sequences to characterise the variation within, and between, epidemic and endemic V. cholerae. We show that, during the 1992–1998 cholera epidemic, the invariant epidemic clone co-existed alongside highly diverse members of the Vibrio cholerae species in Argentina, and we contrast the clonality of epidemic V. cholerae with the background diversity of local endemic bacteria. Our findings refine and add nuance to our genomic definitions of epidemic and endemic cholera, and are of direct relevance to controlling current and future cholera epidemics

Pathogenic Variants in STXBP1 and in Genes for GABAa Receptor Subunities Cause Atypical Rett/Rett-like Phenotypes

Rett syndrome (RTT) is a neurodevelopmental disorder, affecting 1 in 10,000 girls. Intellectual disability, loss of speech and hand skills with stereotypies, seizures and ataxia are recurrent features. Stringent diagnostic criteria distinguish classical Rett, caused by a MECP2 pathogenic variant in 95% of cases, from atypical girls, 40&ndash;73% carrying MECP2 variants, and rarely CDKL5 and FOXG1 alterations. A large fraction of atypical and RTT-like patients remain without genetic cause. Next Generation Sequencing (NGS) targeted to multigene panels/Whole Exome Sequencing (WES) in 137 girls suspected for RTT led to the identification of a de novo variant in STXBP1 gene in four atypical RTT and two RTT-like girls. De novo pathogenic variants&mdash;one in GABRB2 and, for first time, one in GABRG2&mdash;were disclosed in classic and atypical RTT patients. Interestingly, the GABRG2 variant occurred at low rate percentage in blood and buccal swabs, reinforcing the relevance of mosaicism in neurological disorders. We confirm the role of STXBP1 in atypical RTT/RTT-like patients if early psychomotor delay and epilepsy before 2 years of age are observed, indicating its inclusion in the RTT diagnostic panel. Lastly, we report pathogenic variants in Gamma-aminobutyric acid-A (GABAa) receptors as a cause of atypical/classic RTT phenotype, in accordance with the deregulation of GABAergic pathway observed in MECP2 defective in vitro and in vivo models

Self-reported symptoms and medication side effects influence adherence to highly active antiretroviral therapy in persons with HIV infection

To identify variables predictive of nonadherence to highly active antiretroviral therapy (HAART) and to assess whether self-reported symptoms or medication side effects are related to adherence