Editorial: Current Analytical Trends in Drug Testing in Clinical and Forensic Toxicology

Editorial on the Research Topic: Current Analytical Trends in Drug Testing in Clinical and Forensic Toxicology The articles included in this collection cover novel analytical approaches, including chromatographic and spectrometric methods, and sample preparation techniques for the investigation and analysis of several classes of compounds. These compounds include novel psychoactive substances (NPS) as well as other drugs and substances within the scope of clinical and forensic toxicology, and other fields, such as doping control. Current trends in bioanalysis require the constant development of novel analytical tools, which includes efficient sample collection procedures and adequate sample preparation protocols in order to maximize compound detection, even at trace levels. Taking into account that the number of substances possibly present in a sample are increasing, efficient multi-analyte methods are usually necessary.info:eu-repo/semantics/publishedVersio

Editorial: Current Analytical Trends in Drug Testing in Clinical and Forensic Toxicology

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Estrategias de intervención pedagógica que movilizan los procesos iniciales de lectura y escritura en los alumnos de preescolar

El trabajo busca generar nuevas didácticas en los procesos de adquisición de la lengua escrita en el preescolar y desarrollar estrategias pedagógicas que permitan adquirir los procesos iniciales de lectura y escritura, estas estrategias podrán ser retomadas por maestros para hacer más eficaz el aprendizaje de la lengua escrita en los alumnos

Community-associated methicillin-resistant Staphylococcus aureus in children treated in Uruguay

Introduction: Staphylococcus aureus produces a variety of diseases among children, ranging from skin and soft tissue infections to invasive life-threatening diseases. Since 1990, an increasing number of diseases produced by community-associated methicillin-resistant S. aureus (CA-MRSA) isolates have been reported. The aim of this study was to describe the importance and the microbiological characteristics of S. aureus isolates recovered from children treated at the Hospital Pediátrico del Centro Hospitalario ?Pereira Rossell? (HP-CHPR); focusing on invasive diseases caused by CA-MRSA isolates, as well as some clinical aspects of the diseases they have produced. Methodology: One hundred and twenty-five S. aureus isolates recovered from the HP-CHPR between 2003 and 2006 from children with invasive (n=89) and superficial diseases (n=36) were included. Genotypic and phenotypic characteristics of S. aureus isolates and relevant clinical aspects of each child were studied. Results: CA-MRSA isolates accounted for 73% of all S. aureus recovered from invasive (mainly bone and joint) infections, pneumonia and bacteraemia. The most common CA-MRSA strain recovered from invasive (n=65) and superficial (n=36) diseases had the following features: pulsotype A (type USA1100), SCCmec cassette type IV, Panton-Valentine Leukocidin genes positive, susceptibility to trimethoprim-sulfamethoxazole without the inducible macrolide-lincosamide-streptogramin B (iMLSB) resistance phenotype. No association between genotypic characteristics of invasive CA-MRSA isolates and clinical outcomes was found. Conclusions: CA-MRSA isolates produced a wide spectrum of invasive diseases in a public paediatric hospital between 2003 and 2006. Microbiologic characterization suggests the spread of an adapted CA-MRSA clone lacking erm genesFil: Pardo, Lorena. Universidad de la Republica; UruguayFil: Vola, Magdalena. Universidad de la Republica; UruguayFil: Macedo Viñas, Marina. Universidad de la Republica; UruguayFil: Machado, Virginia. Universidad de la Republica; UruguayFil: Cuello, Dianna. Universidad de la Republica; UruguayFil: Mollerach, Marta Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Castro, Marta. Universidad de la Republica; UruguayFil: Pirez, Catalina. Universidad de la Republica; UruguayFil: Varela, Gustavo. Universidad de la Republica; UruguayFil: Algorta, Gabriela. Universidad de la Republica; Urugua

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) clones from Paraguayan children

Introduction: Staphylococcus aureus is considered one of the most important human pathogens, and its levels of resistance to methicillin have increased even in strains isolated from people without nosocomial risk factors. Molecular analysis is essential for understanding the patterns of dissemination. The objective of this study was to identify community-acquired methicillin-resistant S. aureus (CA-MRSA) clones that infected Paraguayan children patients in two periods of time. Methodology: An observational, descriptive study was designed to determine the genetic variability of 115 isolates of CA-MRSA recovered from children who attended four reference centers in Paraguay between 2009-2010 and 2012-2013. Results: The combined use of Pulsed Field Gel Electrophoresis (PFGE), Multi-Locus Sequencing Typing, Multi-Locus Variable Analysis (MLVA) and Spa typing techniques allowed the identification of two dominant clones: ST30-IV-t019 (77%) and ST5-IV-t311 (10%), and the establishment of the former as the leading cause of CA-MRSA infections in children during the study period. Conclusions: This is the first study that provides epidemiological information as well as microbiological and molecular characteristics of CA-MRSA isolates recovered from children from Asunción and the Central Department of Paraguay.Fil: Rodríguez, Fátima. Universidad Nacional de Asunción; ParaguayFil: Salinas, Claudia. Universidad Nacional de Asunción; ParaguayFil: Fernández, Silvina. Universidad de Buenos Aires; ArgentinaFil: Haim, Maria Sol. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mollerach, Marta Eugenia. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Basualdo, Wilma. Hospital Central Instituto de Previsiín Social; Paraguay. Ministerio de Salud Pública y Bienestar Social; ParaguayFil: Castro, Héctor. Hospital Central Instituto de Previsiín Social; Paraguay. Ministerio de Salud Pública y Bienestar Social; ParaguayFil: Quiñónez, Beatriz. Ministerio de Salud Pública y Bienestar Social; ParaguayFil: Arguello, Rocío. Ministerio de Salud Pública y Bienestar Social; ParaguayFil: Rodríguez, Mónica. Hospital Central Instituto de Previsiín Social; ParaguayFil: Grau, Lorena. Hospital Central Instituto de Previsiín Social; ParaguayFil: Espínola, Carmen. Hospital Central Instituto de Previsiín Social; ParaguayFil: Velázquez, Gladys. Hospital Central Instituto de Previsiín Social; ParaguayFil: Samudio, Gloria. Hospital Nacional, Panama; PanamáFil: Gómez, Gloria. Hospital Nacional, Panama; PanamáFil: Campuzano, Ana. Hospital de Clínicas; ParaguayFil: Ortellado, Juana. Hospital de Clínicas; ParaguayFil: Almada, Patricia. Hospital de Clínicas; ParaguayFil: Guillén, Rosa. Universidad Nacional de Asunción; Paragua

Post-mortem neuropathologic examination of a 5-case series of CAR T-cell treated patients

Introduction: Chimeric antigen receptor (CAR) T-cell therapy is a promising immunotherapy for the treatment of refractory hematopoietic malignancies. Adverse events are common, and neurotoxicity is one of the most important. However, the physiopathology is unknown and neuropathologic information is scarce.Materials and methods: Post-mortem examination of 6 brains from patients that underwent CAR T-cell therapy from 2017 to 2022. In all cases, polymerase chain reaction (PCR) in paraffin blocks for the detection of CAR T cells was performed.Results: Two patients died of hematologic progression, while the others died of cytokine release syndrome, lung infection, encephalomyelitis, and acute liver failure. Two out of 6 presented neurological symptoms, one with extracranial malignancy progression and the other with encephalomyelitis. The neuropathology of the latter showed severe perivascular and interstitial lymphocytic infiltration, predominantly CD8+, together with a diffuse interstitial histiocytic infiltration, affecting mainly the spinal cord, midbrain, and hippocampus, and a diffuse gliosis of basal ganglia, hippocampus, and brainstem. Microbiological studies were negative for neurotropic viruses, and PCR failed to detect CAR T -cells. Another case without detectable neurological signs showed cortical and subcortical gliosis due to acute hypoxic-ischemic damage. The remaining 4 cases only showed a mild patchy gliosis and microglial activation, and CAR T cells were detected by PCR only in one of them.Conclusions: In this series of patients that died after CAR T-cell therapy, we predominantly found non-specific or minimal neuropathological changes. CAR T-cell related toxicity may not be the only cause of neurological symptoms, and the autopsy could detect additional pathological findings

Deep-Sequencing Reveals Broad Subtype-Specific HCV Resistance Mutations Associated with Treatment Failure

[Abstract] A percentage of hepatitis C virus (HCV)-infected patients fail direct acting antiviral (DAA)-based treatment regimens, often because of drug resistance-associated substitutions (RAS). The aim of this study was to characterize the resistance profile of a large cohort of patients failing DAA-based treatments, and investigate the relationship between HCV subtype and failure, as an aid to optimizing management of these patients. A new, standardized HCV-RAS testing protocol based on deep sequencing was designed and applied to 220 previously subtyped samples from patients failing DAA treatment, collected in 39 Spanish hospitals. The majority had received DAA-based interferon (IFN) α-free regimens; 79% had failed sofosbuvir-containing therapy. Genomic regions encoding the nonstructural protein (NS) 3, NS5A, and NS5B (DAA target regions) were analyzed using subtype-specific primers. Viral subtype distribution was as follows: genotype (G) 1, 62.7%; G3a, 21.4%; G4d, 12.3%; G2, 1.8%; and mixed infections 1.8%. Overall, 88.6% of patients carried at least 1 RAS, and 19% carried RAS at frequencies below 20% in the mutant spectrum. There were no differences in RAS selection between treatments with and without ribavirin. Regardless of the treatment received, each HCV subtype showed specific types of RAS. Of note, no RAS were detected in the target proteins of 18.6% of patients failing treatment, and 30.4% of patients had RAS in proteins that were not targets of the inhibitors they received. HCV patients failing DAA therapy showed a high diversity of RAS. Ribavirin use did not influence the type or number of RAS at failure. The subtype-specific pattern of RAS emergence underscores the importance of accurate HCV subtyping. The frequency of “extra-target” RAS suggests the need for RAS screening in all three DAA target regions.Ministerio de Economía y Empresa; IDI-20151125Ministerio de Ciencia, Innovación y Universidades; SAF SAF 2017-87846-

Genome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patients

Objectives The analysis of annotated transcripts from genome-wide expression studies may help to understand the pathogenesis of complex diseases, such as systemic sclerosis (SSc). We performed a whole blood (WB) transcriptome analysis on RNA collected in the context of the European PRECISESADS project, aiming at characterising the pathways that differentiate SSc from controls and that are reproducible in geographically diverse populations. Methods Samples from 162 patients and 252 controls were collected in RNA stabilisers. Cases and controls were divided into a discovery (n=79+163; Southern Europe) and validation cohort (n=83+89; Central-Western Europe). RNA sequencing was performed by an Illumina assay. Functional annotations of Reactome pathways were performed with the Functional Analysis of Individual Microarray Expression (FAIME) algorithm. In parallel, immunophenotyping of 28 circulating cell populations was performed. We tested the presence of differentially expressed genes/pathways and the correlation between absolute cell counts and RNA transcripts/FAIME scores in regression models. Results significant in both populations were considered as replicated. Results Overall, 15 224 genes and 1277 functional pathways were available; of these, 99 and 225 were significant in both sets. Among replicated pathways, we found a deregulation in type-I interferon, Toll-like receptor cascade, tumour suppressor p53 protein function, platelet degranulation and activation. RNA transcripts or FAIME scores were jointly correlated with cell subtypes with strong geographical differences; neutrophils were the major determinant of gene expression in SSc-WB samples. Conclusions We discovered a set of differentially expressed genes/pathways validated in two independent sets of patients with SSc, highlighting a number of deregulated processes that have relevance for the pathogenesis of autoimmunity and SSc.EU/EFPIA/Innovative Medicines Initiative Joint Undertaking PRECISESADS 115 56

Rationale, design and preliminary results of the GALIPEMIAS study (prevalence and lipid control of familial dyslipidemia in Galicia, northwest Spain)

[Abstract] Aims. There is little information on the familial nature of dyslipidemias in the Spanish population. This knowledge could have potential diagnostic and treatment implications. The objective of the GALIPEMIAS study was to determine the prevalence of familial dyslipidemia in Galicia, as well as determine the degree of lipid control in the participants. Prevalence of atherosclerotic cardiovascular disease (ASCVD) was also estimated. This paper presents the design, methodology and selected preliminary results. Methodology. A cross‐sectional study was performed in the population aged ≥18 years using cluster sampling and then random sampling. A sample of 1000 subjects was calculated and divided into three sequential phases with a specific methodology for each one. Phase I: selection of subjects from the general population and collection of informed consent documents; Phase II: collection of data from the digital clinical history to select subjects with dyslipidemia according to study criteria; Phase III: personal interview, blood analysis, family tree, and definitive diagnosis of dyslipidemia. Prevalence of different diseases and active medication was analysed. Corrected prevalence (to the reference population) of different risk factors and ASCVD was estimated. Results. Phase I participation was 89.5%. We extracted complete information from 93% of the participants (Phase II). According to the study′s own criteria, 56.5% (n = 527) of the participants had some form of dyslipidemia and almost 33.7% of them had familial dyslipidemia with autosomal dominant inherit pattern. The corrected prevalence of ASCVD was 5.1% (95% CI 3.1‐7.2). Conclusions. Dyslipidemia was the most prevalent cardiovascular risk factor in our population with an autosomal dominant inheritance pattern in one out of every three dyslipidemia cases. Approximately, 5.1% of the sample population aged ≥18 has suffered an episode of ACVD