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Accumulation of senescent cells (SNCs) with a senescence‐associated secretory phenotype (SASP) has been implicated as a major source of chronic sterile inflammation leading to many age‐related pathologies. Herein, we provide evidence that a bifunctional immunotherapeutic, HCW9218, with capabilities of neutralizing TGF‐β and stimulating immune cells, can be safely administered systemically to reduce SNCs and alleviate SASP in mice. In the diabetic db/db mouse model, subcutaneous administration of HCW9218 reduced senescent islet β cells and SASP resulting in improved glucose tolerance, insulin resistance, and aging index. In naturally aged mice, subcutaneous administration of HCW9218 durably reduced the level of SNCs and SASP, leading to lower expression of pro‐inflammatory genes in peripheral organs. HCW9218 treatment also reverted the pattern of key regulatory circadian gene expression in aged mice to levels observed in young mice and impacted genes associated with metabolism and fibrosis in the liver. Single‐nucleus RNA Sequencing analysis further revealed that HCW9218 treatment differentially changed the transcriptomic landscape of hepatocyte subtypes involving metabolic, signaling, cell‐cycle, and senescence‐associated pathways in naturally aged mice. Long‐term survival studies also showed that HCW9218 treatment improved physical performance without compromising the health span of naturally aged mice. Thus, HCW9218 represents a novel immunotherapeutic approach and a clinically promising new class of senotherapeutic agents targeting cellular senescence‐associated diseases. Bifunctional immunotherapeutic HCW9218 functions as a novel SNC‐reducing and senomorphic agent in mice. Subcutaneous administration of HCW9218 activates NK, innate lymphoid group‐1, and CD8+ T cells, and neutralizes TGF‐ß to reduce senescent cells (SNC‐reducing) and SASP (senomorphic) leading to lower chronic inflammation and restored tissue homeostasis.

Andes virus (ANDV) is a zoonotic Orthohantavirus leading to hantavirus cardiopulmonary syndrome. Although most transmissions occur through environmental exposure to rodent faeces and urine, rare person-to-person transmission has been documented, mainly for close contacts. This study investigates the presence and infectivity of ANDV in body fluids from confirmed cases and the duration of viraemia. In this prospective study, 131 participants with confirmed ANDV infection were enrolled in Chile in a prospective study between 2008 and 2022. Clinical samples (buffy coat, plasma, gingival crevicular fluid [GCF], saliva, nasopharyngeal swabs [NPS], and urine) were collected weekly for 3 weeks together with clinical and epidemiological data. Samples were categorised as acute or convalescent (up to and after 16 days following onset of symptoms). Infectivity of positive fluids was assessed after the culture of samples on Vero E6 cells and use of flow cytometry assays to determine the production of ANDV nucleoprotein. ANDV RNA was detected in 100% of buffy coats during acute phase, declining to 95% by day 17, and to 93% between days 23–29. ANDV RNA in GCF and saliva decreased from 30% and 12%, respectively, during the acute phase, to 12% and 11% during the convalescent phase. Successful infectivity assays of RT-qPCR-positive fluids, including GCF, saliva, NPS, and urine, were observed in 18 (42%) of 43 samples obtained during the acute phase of infection. After re-culture, the capacity to infect Vero E6 cells was maintained in 16 (89%) of 18 samples. Severity was associated with the presence of ANDV RNA in one or more fluids besides blood (odds ratio 2·58 [95% CI 1·42–5·18]). ANDV infection is a systemic and viraemic infection, that affects various organs. The presence of infectious particles in body fluids contributes to our understanding of potential mechanisms for person-to-person transmission, supporting the development of preventive strategies. Detection of ANDV RNA in additional fluids at hospital admission is a predictor of disease severity. National Institutes of Health and Agencia de Investigación y Desarrollo. For the Spanish translation of the abstract see Supplementary Materials section.

This work aimed to study the chemical composition, cholinesterase inhibitory activity, and enantiomeric analysis of the essential oil from the aerial parts (leaves and flowers) of the plant Lepechinia paniculata (Kunth) Epling from Ecuador. The essential oil (EO) was obtained through steam distillation. The chemical composition of the oil was evaluated by gas chromatography, coupled to mass spectrometry (GC–MS) and a flame ionization detector (GC-FID). The analyses led to the identification of 69 compounds in total, of which 40 were found in the leaves and 29 were found in the flowers of the plant. The major components found in the oil were 1,8-Cineole, β-Pinene, δ-3-Carene, α-Pinene, (E)-Caryophyllene, Guaiol, and β-Phellandrene. Flower essential oil showed interesting selective inhibitory activity against both enzymes AChE (28.2 ± 1.8 2 µg/mL) and BuChE (28.8 ± 1.5 µg/mL). By contrast, the EO of the leaves showed moderate mean inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), with IC50 values of 38.2 ± 2.9 µg/mL and 47.4 ± 2.3 µg/mL, respectively.

Bovine tuberculosis (bTB) is a zoonotic disease caused mainly by Mycobacterium bovis, which is associated with major economic losses for milk and meat producers. The objective of this trial was to assess the efficacy of the BCG Russia strain in a cohort study performed under field conditions, with the vaccination of calves in seven dairy farms from a high prevalence area in central Chile. The trial was performed with 501 animals, subcutaneously vaccinated with 2–8 × 105 colony-forming units of BCG, whilst 441 matched control animals received a saline placebo. Peripheral blood was collected at 6, 12 and 18 months post-vaccination, and infection status was determined using the IFNγ release assay in conjunction with the DIVA (Detecting Infected amongst Vaccinated Animals) antigens ESAT-6, CFP-10 and Rv3615c. The BCG vaccine showed a low but significant level of protection of 22.4% (95% CI 4.0 to 36.4) at the end of the trial. However, diverse levels of protection and a variable duration of immunity were observed between trial herds. This diverse outcome could be influenced by the general health condition of calves and their exposition to non-tuberculous mycobacteria. These results suggest that BCG vaccination of dairy calves in a natural transmission setting confers variable protection to animals against bTB in a high prevalence area.

Background This study had two main objectives: firstly, to assess the suitability of the Spanish translation of the Young Person’s Clinical Outcome in Routine Evaluation (YP-CORE) for use in Latin America, and secondly, to investigate its psychometric properties specifically with Ecuadorian adolescents. Methods The research consisted of two phases. In Phase 1, insights were gathered from 19 adolescents and 12 experts regarding their comprehension of the YP-CORE. Based on the feedback received during this phase, a revised version of the YP-CORE was developed. In Phase 2, a psychometric assessment of this modified version was conducted with 298 adolescents in Ecuador, aged 11 to 17 years. Results The psychometric analysis revealed that this adapted version of the YP-CORE demonstrated satisfactory levels of acceptability, internal consistency, and test-retest reliability. The factor analysis favored a two-factor model over a single factor, yet the minimal substantive distinctions between these two factors do not justify the use of subscale scoring. Furthermore, the scores indicated age-related differences, with older adolescents (aged 14 to 17 years) obtaining higher scores, and gender-related variations, with females scoring higher. Conclusions This study addresses the need for, and provides, a Spanish-adapted YP-CORE tailored for use in Latin America. This freely available version has the potential to offer valuable insights into interventions for adolescents in the region and to enhance our understanding of their psychological distress.

The COVID-19 pandemic has prompted a transformation of medical training. Although there were obvious medical education and social interaction challenges, e-learning presented some advantages, which may have generated medical curricula innovation and adjustments to novel technological methodologies. This study aims to generate consensuses among medical students regarding medical education provided during the pandemic in the resource-limited context of a Global South university. The implementation of a participatory Delphi method included a recruitment campaign, training, constitution of Delphi panels and questions, and development of the Delphi exercises. Students from the second to the sixth year of medicine of a university in Quito, Ecuador, constituted two Delphi panels, developed questions about the education received during the pandemic, and answered them over 3.5 rounds. Twenty-two medical students participated in the Delphi exercises about their perception of medical education during the COVID-19 pandemic. The analysis consisted of a total of 22 Delphi questions divided into five distinct categories: adaptations and innovations, curriculum and assessment changes, virtual clinical practice, time management, and mental health. The authors established high, medium, and low consensuses for analysis. Consensuses were reached based on students' academic year and focused on the changes in lecture delivery, the usage of new technologies, patient care skills, the impact of the educational routine, and the mental health of the COVID-19 pandemic. The way the pandemic affected medical education in the Global South set the stage for the need for a comprehensive review of tools, skills, and curricula for students from culturally diverse backgrounds. This study offers a highly replicable methodology to generate consensuses and introduce students to academic research.

Background ANDV is etiologic agent of hantavirus cardiopulmonary syndrome (HCPS) in Chile. Transmission occurs mainly by exposure to aerosolized excretes of infected rodents, person-to-person transmission has also been reported. ANDV infected endothelial cell through αV,β3 integrin at plexin-semaphorin-integrin (PSI) domain. In vitro assays establish that the change from leucine to proline, at residues 33 in PSI-domain inhibits ANDV recognition of integrin. Here we assessed the risk that represents a polymorphism leucine to proline (L33P) and the association to susceptibility to ANDV. Methods For risk assessment, 74 cases and 105 controls (exposed but not infected) were genotyped by Taqman assay, epidemiological and demographic data were recorded. We also evaluated SNP distribution at general population, infected population (serum collection) and 11 prospectively diagnosed ANDV cases. A regression logistic model was used to assess environmental or person to person risks factors of hantavirus infection either in presence or absence of the “susceptible” or “protective” genotypes. Results In cases and controls the susceptible (TT) genotype (Leucine) was distributed in an 89.2 and 60%, respectively (Figure 1). The protective genotype (CC) was absent among cases but present at 11.4% in exposed controls. We estimated the Odds ratio (OR), through a logistic model, first using only previously described risk activities and after adding the genotype TT; the OR increased from 6.2 to 12.6. Cases and control at same exposure (access to abandoned place) showed that controls have a 57% of TT genotype, meanwhile in cases was 91%, with an OR of 7.3. For a second common exposure activities (handle woods) the controls had a 59.4% of TT genotype, meanwhile for cases 85%. For general and infected population both did not show statistical differences in allele distribution, and we detected a 1.7% of CC genotype in the infected population (Figure 2). We did not detected CC genotypes in the eleven prospective ANDV cases. Conclusion There was association between this particular SNP and infection susceptibility to ANDV. We highlight the relevance of genetic background in host-virus interaction. Nevertheless, other factors such as innate immune system or viral variability must be explored to fully understand the disease pathogenesis. Disclosures C. Martinez-Valdebenito, FONDECYT1161197: Grant Investigator, Educational grant. ACT1408: Grant Investigator, Research grant. M. Ferres, FONDECYT1161197: Grant Investigator, Research grant. ACT1408: Grant Investigator, Research grant. N. Le Corre, FONDECYT1161197: Grant Investigator, Research grant. ACT1408: Grant Investigator, Research grant. J. Angulo, FONDECYT1161197: Grant Investigator, Research grant. ACT1408: Grant Investigator, Research grant.