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    TGFβ links EBV to multisystem inflammatory syndrome in children
    (Springer Science and Business Media LLC, 2025-03-12)
    Carl Christoph Goetzke
    ;
    Mona Massoud
    ;
    Stefan Frischbutter
    ;
    Gabriela Maria Guerra
    ;
    Marta Ferreira-Gomes
    <jats:title>Abstract</jats:title> <jats:p>In a subset of children and adolescents, SARS-CoV-2 infection induces a severe acute hyperinflammatory shock<jats:sup>1</jats:sup> termed multisystem inflammatory syndrome in children (MIS-C) at four to eight weeks after infection. MIS-C is characterized by a specific T cell expansion<jats:sup>2</jats:sup> and systemic hyperinflammation<jats:sup>3</jats:sup>. The pathogenesis of MIS-C remains largely unknown. Here we show that acute MIS-C is characterized by impaired reactivation of virus-reactive memory T cells, which depends on increased serum levels of the cytokine TGFβ resembling those that occur during severe COVID-19 (refs. <jats:sup>4,5</jats:sup>). This functional impairment in T cell reactivity is accompanied by the presence of TGFβ-response signatures in T cells, B cells and monocytes along with reduced antigen-presentation capabilities of monocytes, and can be reversed by blocking TGFβ. Furthermore, T cell receptor repertoires of patients with MIS-C exhibit expansion of T cells expressing TCRVβ21.3, resembling Epstein–Barr virus (EBV)-reactive T cell clones capable of eliminating EBV-infected B cells. Additionally, serum TGFβ in patients with MIS-C can trigger EBV reactivation, which is reversible with TGFβ blockade. Clinically, the TGFβ-induced defect in T cell reactivity correlates with a higher EBV seroprevalence in patients with MIS-C compared with age-matched controls, along with the occurrence of EBV reactivation. Our findings establish a connection between SARS-CoV-2 infection and COVID-19 sequelae in children, in which impaired T cell cytotoxicity triggered by TGFβ overproduction leads to EBV reactivation and subsequent hyperinflammation.</jats:p>
    Scopus© Citations 4  2
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    Performance of the VITEK® MS system for the identification of filamentous fungi in a microbiological laboratory in Chile
    (Public Library of Science (PLoS), 2024-12-23) ;
    Rodrigo Cruz
    ;
    Pérez Villa, Inia
    ;
    Carmen Varela
    ;
    Cristina Díaz
    <jats:p>Filamentous fungi are an emergent cause of severe infections in immunocompromised patients. Timely and accurate identification is crucial to initiate appropriate therapy. Traditional identification methods are time-consuming, labor-intensive, and operator-dependent. Matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectrometry is a rapid and easy-to-perform identification method. The effectiveness of a commercial MALDI-TOF MS platform to identify filamentous fungi in a clinical laboratory was evaluated. The study included 67 fungal isolates from 35 species/species complexes, which were identified and confirmed in mycology reference laboratories; 32 derived from clinical samples, 34 from strain collections and one was an ATCC strain. The study used the VITEK<jats:sup>®</jats:sup> MS system (v3.2.0 database), after sample extraction by VITEK<jats:sup>®</jats:sup> MS Mould Kit. Results were classified as “correct species”, “correct species complex”, “correct genus”and “no identification”. VITEK<jats:sup>®</jats:sup> MS correctly identified 91.0% of isolates (58.2% to species, 29.9% to species complex, and 1.5% to genus level only). In 82%, the result matched the species/species complex identified by reference methods. No misidentifications were observed. The kit was rapid and easy to use. In conclusion, the VITEK<jats:sup>®</jats:sup> MS system showed a high capability to accurately identify filamentous fungi in a clinical laboratory.</jats:p>
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    Hosts and vectors of scrub typhus in Chile: epidemiological study and molecular analyses of Orientia infection in rodents and rodent-associated mites
    (Springer Science and Business Media LLC, 2024-12-18)
    Constanza Martínez-Valdebenito
    ;
    Gerardo Acosta-Jamett
    ;
    Rayitray Abello
    ;
    Ju Jiang
    ;
    Allen L. Richards
    <jats:title>Abstract</jats:title><jats:p><jats:italic>Candidatus</jats:italic> Orientia chiloensis causes scrub typhus over a wide geographical range in southern Chile. The life cycle, including vectors and reservoirs of this novel rickettsial pathogen, is incompletely understood. We analyzed rodent tissue and rodent-associated mite samples collected during a field study in six localities on Chiloé Island, where human scrub typhus cases have occurred. Using molecular methods, we detected <jats:italic>Orientia</jats:italic> DNA in 24.8% of rodents, belonging to five of seven captured species. <jats:italic>Orientia</jats:italic>-infection rates showed geographical variations, but were not influenced by rodent species, sex, age, and mite infestation. Phylogenetic analysis showed that <jats:italic>Orientia</jats:italic> sequences from trombiculid mites (<jats:italic>Proschoengastia eloisae</jats:italic>) were identical to those from scrub typhus patients from the same region. The results suggest that these rodent-associated mites serve as vectors and play an important role in the ecology of scrub typhus in southern Chile. Further studies are required to determine whether <jats:italic>Orientia</jats:italic>-infected rodents can also serve as reservoir of <jats:italic>Orientia</jats:italic> in Chile.</jats:p> <jats:p><jats:bold>Graphical Abstract</jats:bold></jats:p>
      1Scopus© Citations 8
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    Microbial Community and Enzyme Activity of Forest Plantation, Natural Forests, and Agricultural Land in Chilean Coastal Cordillera Soils
    (2023)
    Yessica Rivas
    ;
    Humberto Aponte
    ;
    ;
    Francisco Matus
    ;
    Oscar Martínez
    <jats:p>Despite the global expansion of forest plantations in Chile, their effect on biology properties of soil has still been only scarcely studied. Land use change in the Chilean Coastal Cordillera (36° to 40° S) is mainly attributed to the conversion of native forest to agriculture and forest plantations (Eucalyptus globulus and Pinus radiata de Don). The aim of this paper was to evaluate the changes in microbial composition (PCR-DGGE) and enzyme activity after the substitution of a native forest (e.g., Nothofagus spp.) by fast-growing exotic species and cropping. The most important factors that influence the abundance and diversity of bacteria and the fungi community were the soil organic matter (SOM) content, phosphorous (P-Olsen), calcium (Ca), boron (B), and water-holding capacity. These variables can better predict the microbial community composition and its enzymatic activity in the surface Ah horizon. Land use change also affected chemical soil properties of biogeochemical cycles. However, to deeply understand the connection between chemical and physical soil factors and microbial community composition, more research is needed. On the other hand, the expansion of forest plantations in Chile should be subject to legislation aimed to protect the biological legacy as a strategy for forest productivity as well as the soil microbial biodiversity.</jats:p>
      2Scopus© Citations 5
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    High Burden of Intestinal Colonization With Antimicrobial-Resistant Bacteria in Chile: An Antibiotic Resistance in Communities and Hospitals (ARCH) Study
    (2023) ;
    Rachel M Smith
    ;
    Ashley Styczynski
    ;
    Felipe Sánchez
    ;
    Lea Maureira
    <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Antimicrobial resistance is a global threat, heavily impacting low- and middle-income countries. This study estimated antimicrobial-resistant gram-negative bacteria (GNB) fecal colonization prevalence in hospitalized and community-dwelling adults in Chile before the coronavirus disease 2019 pandemic.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>From December 2018 to May 2019, we enrolled hospitalized adults in 4 public hospitals and community dwellers from central Chile, who provided fecal specimens and epidemiological information. Samples were plated onto MacConkey agar with ciprofloxacin or ceftazidime added. All recovered morphotypes were identified and characterized according to the following phenotypes: fluoroquinolone-resistant (FQR), extended-spectrum cephalosporin-resistant (ESCR), carbapenem-resistant (CR), or multidrug-resistant (MDR; as per Centers for Disease Control and Prevention criteria) GNB. Categories were not mutually exclusive.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>A total of 775 hospitalized adults and 357 community dwellers were enrolled. Among hospitalized subjects, the prevalence of colonization with FQR, ESCR, CR, or MDR-GNB was 46.4% (95% confidence interval [CI], 42.9–50.0), 41.2% (95% CI, 37.7–44.6), 14.5% (95% CI, 12.0–16.9), and 26.3% (95% CI, 23.2–29.4). In the community, the prevalence of FQR, ESCR, CR, and MDR-GNB colonization was 39.5% (95% CI, 34.4–44.6), 28.9% (95% CI, 24.2–33.6), 5.6% (95% CI, 3.2–8.0), and 4.8% (95% CI, 2.6–7.0), respectively.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>A high burden of antimicrobial-resistant GNB colonization was observed in this sample of hospitalized and community-dwelling adults, suggesting that the community is a relevant source of antibiotic resistance. Efforts are needed to understand the relatedness between resistant strains circulating in the community and hospitals.</jats:p> </jats:sec>
    Scopus© Citations 10  2
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    Scopus© Citations 13  2
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    CRISPR/Cas13-Based Platforms for a Potential Next-Generation Diagnosis of Colorectal Cancer through Exosomes Micro-RNA Detection: A Review
    (2021)
    Benjamín Durán-Vinet
    ;
    Karla Araya-Castro
    ;
    ;
    Luis Vergara
    ;
    Helga Weber
    <jats:p>Colorectal cancer (CRC) is the third most prevalent cancer with the second highest mortality rate worldwide. CRC is a heterogenous disease with multiple risk factors associated, including obesity, smoking, and use of alcohol. Of total CRC cases, 60% are diagnosed in late stages, where survival can drop to about 10%. CRC screening programs are based primarily on colonoscopy, yet this approach is invasive and has low patient adherence. Therefore, there is a strong incentive for developing molecular-based methods that are minimally invasive and have higher patient adherence. Recent reports have highlighted the importance of extracellular vesicles (EVs), specifically exosomes, as intercellular communication vehicles with a broad cargo, including micro-RNAs (miRNAs). These have been syndicated as robust candidates for diagnosis, primarily for their known activities in cancer cells, including immunoevasion, tumor progression, and angiogenesis, whereas miRNAs are dysregulated by cancer cells and delivered by cancer-derived exosomes (CEx). Quantitative polymerase chain reaction (qPCR) has shown good results detecting specific cancer-derived exosome micro-RNAs (CEx-miRNAs) associated with CRC, but qPCR also has several challenges, including portability and sensitivity/specificity issues regarding experiment design and sample quality. CRISPR/Cas-based platforms have been presented as cost-effective, ultrasensitive, specific, and robust clinical detection tools in the presence of potential inhibitors and capable of delivering quantitative and qualitative real-time data for enhanced decision-making to healthcare teams. Thereby, CRISPR/Cas13-based technologies have become a potential strategy for early CRC diagnosis detecting CEx-miRNAs. Moreover, CRISPR/Cas13-based platforms’ ease of use, scalability, and portability also showcase them as a potential point-of-care (POC) technology for CRC early diagnosis. This study presents two potential CRISPR/Cas13-based methodologies with a proposed panel consisting of four CEx-miRNAs, including miR-126, miR-1290, miR-23a, and miR-940, to streamline novel applications which may deliver a potential early diagnosis and prognosis of CRC.</jats:p>
      7Scopus© Citations 22
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    Seroprevalence of Natural and Acquired Immunity against the SARS-CoV-2 Virus in a Population Cohort from Two Chilean Cities, 2020–2022
    (2023)
    Loreto Núñez-Franz
    ;
    Muriel Ramírez-Santana
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    ;
    Macarena Said
    ;
    <jats:p>Background: Chile has achieved the highest coverage for vaccines against the SARS-CoV-2 virus worldwide. Objective: To assess the progression of immunity (natural and acquired by vaccine) in a cohort from two Chilean cities. Methods: Individuals (n = 386) who participated in three phases of population-based serial prevalence studies were included (2020–2021 and 2022). Presence of SARS-CoV-2 antibodies was measured in serum. Data including time of vaccination and type of vaccine received were analysed with descriptive statistics. Results: Seroprevalence was 3.6% in the first round and increased to 96.9% in the second and 98.7% in the third. In the third round, 75% of individuals who had received the basal full scheme were seropositive at 180 days or more since their last dose; 98% of individuals who received one booster dose were seropositive at 180 days or more, and 100% participants who received two boosters were seropositive, regardless of time since their last dose. Participants receiving mRNA vaccines had higher seroprevalence rates over time. Conclusions: The high vaccination coverage in Chile enabled the population to maintain high levels of antibodies. Vaccination boosters are essential to maintain immunity over time, which also depends on the type of vaccine administered.</jats:p>
      1Scopus© Citations 12
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    Indirect effect of COVID-19 on maternal mortality in Chile
    (2023)
    Rogelio Gonzalez
    ;
    Mario Merialdi
    ;
    Paola Viviani
    ;
    María Teresa Haye
    ;
    Giorgia Cartes
    Scopus© Citations 2  2