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NLC-Based Rifampicin Delivery System: Development and Characterization for Improved Drug Performance Against Staphylococcus aureus
(2025) Carrasco, Javiera; Sandoval, Felipe; Schuh, Christina; Lagos, Carlos; Morales, Javier; Arriagada, Francisco; Ortiz, Andrea
Background/Objectives: Rifampicin is a typical antibiotic used for the treatment of Staphylococcus aureus (S. aureus) infections; however, its clinical utility is limited by poor aqueous solubility, chemical instability, and increasing bacterial resistance. Nanostructured lipid carriers (NLCs) offer a promising strategy to improve drug solubility, stability, and antimicrobial performance. Methods: In this study, rifampicin-loaded NLC (NLC-RIF) was developed using a hot homogenization with a low energy method and characterized in terms of particle size, polydispersity index, zeta potential, encapsulation efficiency, colloidal stability, and drug loading. Results: In vitro release studies under sink conditions demonstrated a biphasic release pattern, best described by the Korsmeyer-Peppas model, suggesting a combination of diffusion and matrix erosion mechanisms. Antimicrobial activity against S. aureus revealed a substantial increase in potency for NLC-RIF, with an IC50 of 0.46 ng/mL, approximately threefold lower than that of free rifampicin. Cytotoxicity assays in HepG2 cells confirmed over 90% cell viability across all tested concentrations. Conclusions: These findings highlight the potential of NLC-RIF as a biocompatible and effective nanocarrier system for enhancing rifampicin delivery and antibacterial activity.
Norma técnica de prevención de transmisión vertical de hepatitis B. 2022
(2022) González, Fernando; Contreras, Patricia; Peña, Andrea; Izquierdo, Giannina; Zamora, Francisco; Zapata, Rodrigo; Muñoz, María; Peña, Andrea; Jara, Ana; Torres, Claudio; Alicia, Ribes; Torrealba, Paulina
La infección por el virus de la hepatitis B (VHB) es un problema de gran impacto en la salud pública en el mundo1. Aproximadamente un tercio de la población mundial ha estado expuesta al virus y entre 250 a 290 millones de personas tienen infección crónica por VHB (persistencia de HBsAg por al menos 6 meses). La Organización Mundial de la Salud estimó para el año 2019 aproximadamente 820.000 defunciones, debido a complicaciones del VHB como cirrosis o carcinoma hepatocelular2.
Betulinic Acid ω-Triphenylphosphonium Alkyl Esters: Antiproliferative Activities and In Silico Pharmacokinetic Profiles
(2025) Suárez, Cristian; Duarte, Claudia; Gajardo, Javier; Salgado, Paola; Salas, Julio; Cassels, Bruce; Theoduloz, Cristina; Jara, José; Fuentes, Sebastián; Campodónico, Paola; Soto, Jorge; Catalán, Mabel
Betulinic acid (BA) and some derivatives are well-known antiproliferative compounds. Literature precedents suggest that incorporating triphenylphosphonium (TPP+) salts on this triterpenoid scaffold enhances its biological activity. In the present study, we carried out a simple synthesis of C-28 ester derivatives of this triterpenoid conjugated with TPP+ bromide salts through 4- to 6-carbon chains via nucleophilic substitution of the corresponding ω-TPP+bromoalkanes. Tests for antiproliferative activity in nine cancer cell lines and normal human fibroblasts showed that TPP+ incorporation enhanced the potency of BA by more than an order of magnitude, up to 100-fold. BA-C4-TPP+Br-, with a four-carbon chain separating the TPP+ moiety from the BA, showed remarkable antiproliferative effects, sometimes more potent than the reference drug (Etoposide). This compound exhibited the strongest mitochondrial uncoupling effect in human cancer cells. No significant LDH release was noted in colorectal carcinoma cells at low micromolar concentrations of BA-C4-TPP+Br-, and sub-micromolar concentrations were sufficient for inducing apoptosis. The in silico prediction of pharmacokinetic properties suggested high oral absorption (88%), as well as a non-inhibitor and non-substrate profile vs. cytochrome isoenzymes. These results point to this compound as a promising lead for the development of novel anticancer drugs.
Antimicrobial Resistance in the Aconcagua River, Chile: Prevalence and Characterization of Resistant Bacteria in a Watershed Under High Anthropogenic Contamination Pressure
(2025) González, Nicolás; Lira, Diego; Covarrubia, Richard; Plaza, Johan; Munita, Jose M.; Carter, Mauricio; Olivares, Jorge
Background: Antimicrobial resistance (AMR) is a growing global health concern, driven in part by the environmental release of antimicrobial-resistant bacteria (ARB) and antimicrobial resistance genes (ARGs). Aquatic systems, particularly those exposed to urban, agricultural, and industrial activity, are recognized as hotspots for AMR evolution and transmission. In Chile, the Aconcagua River-subject to multiple anthropogenic pressures-offers a representative model for studying the environmental dimensions of AMR. Methods: Thirteen surface water samples were collected along the Aconcagua River basin in a single-day campaign to avoid temporal bias. Samples were filtered through 0.22 μm membranes and cultured on MacConkey agar, either unsupplemented or supplemented with ceftazidime (CAZ) or ciprofloxacin (CIP). Isolates were purified and identified using MALDI-TOF mass spectrometry. Antibiotic susceptibility was evaluated using the Kirby-Bauer disk diffusion method in accordance with CLSI guidelines. Carbapenemase activity was assessed using the Blue-Carba test, and PCR was employed for the detection of the blaVIM, blaKPC, blaNDM, and blaIMP genes. Results: A total of 104 bacterial morphotypes were isolated; 80 were identified at the species level, 5 were identified at the genus level, and 19 could not be taxonomically assigned using MALDI-TOF. Pseudomonas (40 isolates) and Aeromonas (25) were the predominant genera. No growth was observed on CIP plates, while 24 isolates were recovered from CAZ-supplemented media, 87.5% of which were resistant to aztreonam. Five isolates exhibited resistance to carbapenems; two tested positive for carbapenemase activity and carried the blaVIM gene. Conclusions: Our results confirm the presence of clinically significant resistance mechanisms, including blaVIM, in environmental Pseudomonas spp. from the Aconcagua River. These findings highlight the need for environmental AMR surveillance and reinforce the importance of adopting a One Health approach to antimicrobial stewardship and wastewater regulation.
Conserved missense variant pathogenicity and correlated phenotypes across paralogous genes
(2025) Brünger, Tobias; Ivaniuk, Alina; Pérez Palma, Eduardo; Montanucci, Ludovica; Cohen, Stacey; Smith, Lacey; Parthasarathy, Shridhar; Helbig, Ingo; Nothnagel, Michael; May, Patrick; Lal, Dennis
Background: The majority of missense variants in clinical genetic tests are classified as variants of uncertain significance. Prior research shows that the deleterious effects and the subsequent molecular consequences of variants are often conserved among paralogous protein sequences within a gene family. Here, we systematically quantify on an exome-wide scale whether the existence of pathogenic variants in paralogous genes at a conserved position can serve as evidence for the pathogenicity of a new variant. For the gene family of voltage-gated sodium channels, where variants and expert-curated clinical phenotypes are available, we also assess whether phenotype patterns of multiple disorders for each gene are conserved across variant positions within the gene family.
Results: Mapping 590,000 pathogenic and 1.9 million population variants onto 9928 genes grouped into 2054 paralogous families increases the number of residues with classifiable evidence 5.1-fold compared with gene-specific data alone. The presence of a pathogenic variant in a paralogous gene is associated with a positive likelihood ratio of 13.0 for variant pathogenicity. Across ten genes encoding voltage-gated sodium channels and 22 expert-curated disorders, we identify cross-paralog correlated phenotypes based on 3D structure spatial position. For example, multiple established loss-of-function related disorders across SCN1A, SCN2A, SCN5A, and SCN8A show overlapping spatial variant clusters. Finally, we show that phenotype integration in paralog variant selection improves variant classification.
Conclusion: Conserved pathogenic missense variants in paralogous genes provide robust, quantifiable support for clinical variant interpretation, and phenotype-informed mapping further improves predictions.
Long-term effects of COVID-19 in patients with primary immunodeficiency: An IPOPI worldwide survey
(2025) Van Leeuwen, Leanne; Van Coillie, Samya; Prévot, Johan; Drabwell, Jose; Mahlaoui, Nizar; Sánchez-Ramón, Silvia; Poli Harlowe, María Cecilia; Meyts, Isabelle; Ali, Adli; Lowe, David; Dalm, Virgil; Pergent, Martine
Background: During the coronavirus disease 2019 (COVID-19) pandemic, many individuals developed persistent symptoms after COVID-19. The data on these long-term effects in the primary immunodeficiency (PID) community are limited.
Objective: This study aimed to understand long-term symptoms after COVID-19 in patients with PID, focusing on prevalence, risk factors, viral persistence, and the impact of COVID-19 on their health-related quality of life (HR-QoL).
Methods: A global, multilingual web-based survey was conducted by the International Patient Organization for Primary Immunodeficiencies between July and October 2023. Self-reported data on demographics, PID diagnosis, comorbidities, COVID-19, and HR-QoL were collected using the EuroQol 5-Dimensions 5-Level (EQ-5D-5L) survey and analyzed.
Results: Of the 1160 respondents, 25% reported persistent symptoms after COVID-19. Common symptoms included fatigue, headache, and nasal symptoms. Compared with those respondents without persistent symptoms, those with persistent symptoms after COVID-19 reported a significantly higher prevalence of symptoms across all categories-systemic, pain, cardiopulmonary, gastrointestinal, neurologic, psychological, neurocognitive, and others-except for upper respiratory tract symptoms. Independent risk factors for development of persistent symptoms included female sex, asthma, neurologic diseases, and predominantly antibody deficiency other than common variable immunodeficiency or agammaglobulinemia. In 30% of patients with persistent symptoms, viral clearance was not achieved within 1 month. During the pandemic, HR-QoL declined across all PID categories-even in those without COVID-19, but especially in those with a symptom duration of more than 6 months.
Conclusion: Persistent symptoms after COVID-19 are prevalent among patients with PID, with various risk factors identified. The COVID-19 pandemic had a considerable impact on the HR-QoL of patients with PID regardless of COVID-19 status.
Case-fatality of acute ischemic stroke in stroke units of Latin American hospitals
(2025) Vences, Miguel; Barboza, Miguel; Carbonera, Leonardo; Failoc, Virgilio; Rosales, Julieta; Amaya, Pablo; Lavados, Pablo; FAICAM Registry Group
Background and purpose: The Case-fatality of acute ischemic stroke in stroke units of Latin American hospitals is a multicenter registry from various stroke centers in Latin America, exploring demographic, clinical, imaging, and functional outcomes in acute ischemic stroke (AIS) patients, with the intention of determining case-fatality rates (in-hospital, 30 and 90 days follow up) and analyzing associated risk factors.
Methods: We conducted a retrospective cohort study using data from hospitalized AIS patients over 18 years of age, collected from 27 centers in 11 Latin American countries between January 1 and December 31, 2022. The effect size was estimated using the hazard ratio (HR) and 95 % confidence intervals (95 % CI) through Cox regression models to assess the association between time to 30-day fatality event and covariates.
Results: A total of 2,997 patients were included. The mean age was 68.7 years and 48.1 % were women. In-hospital case-fatality was 9.42 %, 277 patients (10.2 %) died within 30 days, and 90-day case-fatality was relatively close at 353 patients (13.3 %). Complications were reported in 31.3 % of cases, most frequently infections (18.5 %). Age over 75 years (HRa=2.28), hyperglycemia (HRa=1.28), baseline status (HRa=1.61), stroke severity according to NIHSS >26 (HRa=6.11) and the presence of neurological complications (HRa=3.2) were risk factors for 30-day follow up case-fatality in these patients.
Conclusion: AIS patients in Latin America stroke centers had an in-hospital case-fatality of 9.42 % and the 30-day case-fatality was 10.2 %. Older age, hyperglycemia, baseline status, stroke severity and neurological complications were the strongest predictors of early case-fatality. The findings underscore the need to optimize stroke management protocols in the region.
Colonization with antibiotic resistant bacteria in communities and hospitals across six countries, including Bangladesh, Botswana, Chile, Guatemala, India, and Kenya
(2025) Parra, Gemma; Lautenbach, Ebbing; Mosepele, Mosepele; Mannathoko, Naledi; Gross, Robert; Call, Douglas; Ramay, Brooke; Omulo, Sylvia; Girish, C P; Bhatnagar, Tarun; Chowdhury, Fahmida; Syeda Mah-E-Muneer; Araos Bralic, Rafael Ignacio; Munita, Jose M.; Acevedo, Johanna; Mahon, Garrett; Smith, Rachel; Styczynski, Ashley
The recognized burden of antimicrobial resistance (AR) is greatest in low- and middle-income countries (LMICs), but limitations in surveillance preclude accurate estimates of AR. We aimed to evaluate colonization in communities and hospitals across six LMICs for two clinically-important pathogens: extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) and carbapenem-resistant Enterobacterales (CRE). Participants in hospitals and communities provided rectal swabs or stool samples for ESCrE and CRE identification. Isolates recovered from selective agars underwent confirmatory identification and antibiotic susceptibility testing (AST) using Vitek® 2, MALDI-TOF, and/or disc diffusion testing. ESCrE and CRE were defined based on established breakpoints of phenotypic resistance to third-generation cephalosporins and carbapenems, respectively, to calculate prevalence of colonization. Community prevalence estimates were weighted to account for sampling design differences. A total of 10,139 participants across the 6 countries provided samples; 63% were females with a median age of 35 years (range: 0-99). Colonization with ESCrE in hospitals was high in all sites (range 34-84%). In communities, ESCrE colonization ranged from 22 to 77%. Prevalence of CRE colonization in hospitals ranged from 7 to 36% and in communities ranged from < 1 to 14%. These findings reveal a high burden of AR colonization in LMICs in both communities and hospitals. Cost-effective strategies to reduce AR colonization burden are needed in LMICs.
HSV-1 alters lipid metabolism and induces lipid droplet accumulation in functionally impaired mouse dendritic cells
(2025) Farías, Mónica; Cancino, Felipe; Navarro, Areli; Duarte, Luisa; Soto, Abel; Tognarelli, Eduardo; Ramm, Maximiliano; Alarcón, Bárbara; Cordero, José; San Martín, Sergio; Agurto, Cristian; Retamal, Angello; Riedel, Claudia; Barrera, Nelson; Bustamante, Luis; Bueno, Susan; Kalergis, Alexis; González, Pablo
Herpes simplex virus type 1 (HSV-1) significantly impairs dendritic cell (DC) function, ultimately eliciting the death of these cells. Here, we sought to assess whether HSV-1 modulates lipid metabolism in mouse DCs as a mechanism of immune evasion. For this, we performed RT-qPCR gene arrays with ingenuity pathway analysis (IPA), RNA sequencing (RNA-seq) and gene set enrichment analysis (GSEA), confocal microscopy, transmission electron microscopy, ultra-high-performance liquid chromatography-quadrupole time-of-flight (UHPLC-QTOF) analysis, pharmacological inhibition of eight lipid-metabolism-related enzymes in HSV-1-infected DCs, co-cultures between virus-specific transgenic CD4+ and CD8+ T cells and HSV-1-infected DCs, and in vivo assays with mice. We found that HSV-1 significantly alters lipid metabolism in DCs and induces lipid droplet (LD) accumulation in these cells. Pharmacological inhibition of two particular lipid metabolism enzymes was found to partially restore DC function. Overall, these results suggest that lipid metabolism plays an important role in the impairment of DC function by HSV-1.
Pericarditis constrictiva tuberculosa de rápida progresión y fatal
(2026) Sanhueza, Renato; Di Giammarino, Antonia; Fuentes, Cristóbal; Descalzi, Sofía; Follegati, Micaela; Roca, Felipe; Saldias, Roberto
Objetivo: Describir caso de pericarditis constrictiva secundaria a tuberculosis de evolución fulminante, destacando hallazgos clínicos, microbiológicos, imagenológicos e histopatológicos. Metodología: Estudio observacional, descriptivo y retrospectivo, consistente en un reporte de caso. La información se obtuvo de fuentes como ficha clínica, exámenes de laboratorio, estudios microbiológicos e imagenológicos, entre otros. Los antecedentes se ordenaron cronológicamente y analizaron descriptivamente. Se obtuvo firma de consentimiento informado del representante legal. Desarrollo: Hombre de 28 años con consumo perjudicial de alcohol y policonsumo de sustancias, con lesión cervical abscedada crónica interpretada como probable escrófula. Consultó por ascitis progresiva, edema periférico, pérdida de peso, sudoración nocturna y disnea. La tomografía computarizada evidenció derrame pericárdico y pleural bilateral, además de congestión hepática. Inicialmente fue manejado como pericarditis viral; luego presentó tromboembolismo pulmonar, shock refractario y falla respiratoria, requiriendo ventilación mecánica y soporte vasoactivo. La ecocardiografía mostró fisiología constrictiva y engrosamiento pericárdico. Durante la toracotomía se observó un pericardio tabicado con contenido hemopurulento. La PCR para Mycobacterium tuberculosis en líquido pericárdico fue positiva y la biopsia evidenció inflamación granulomatosa. Pese al drenaje quirúrgico y al tratamiento antituberculoso, el paciente falleció. Discusión: La presentación inespecífica y el bajo rendimiento microbiológico de las muestras pericárdicas pueden retrasar el diagnóstico. Los síntomas constitucionales, el derrame pericárdico y las manifestaciones extrapulmonares deben aumentar la sospecha de tuberculosis. Conclusión: La integración precoz de antecedentes clínicos y hallazgos imagenológicos, microbiológicos e histopatológicos son fundamental para establecer el diagnóstico e iniciar tratamiento oportuno, aunque las formas avanzadas de tuberculosis pueden evolucionar fatalmente.
Geographic divergence of methicillin-resistant Staphylococcus aureus ST5-SCCmecI in the aftermath of a major earthquake and tsunami: impact of a plasmid harboring heavy metal resistance genes
(2025) Martínez, Jose; Alcalde, Manuel; Jara, Estefanía; Reyes, Jinnethe; Carvajal, Lina; Rincon, Sandra; Ríos, Rafael; Diaz, Lorena; Quesille, Ana; Riquelme, Roberto; Rivas Jiménez, Lina María; Moustafa, Ahmed; Hanson, Blake; Undurraga, Eduardo; Olivares, Jorge; García, Patricia; Araos Bralic, Rafael Ignacio; Planet, Paul; Arias, César; Munita, Jose M.
El Staphylococcus aureus resistente a la meticilina (SARM) es una importante amenaza para la salud pública. La propagación global del SARM se caracteriza por sucesivas oleadas de clones epidémicos que dominan regiones geográficas específicas. Se cree que la adquisición de genes que codifican la resistencia a metales pesados (GMMP) es una característica clave en la divergencia geográfica del SARM. Sin embargo, la relación causa-efecto entre la presencia de GMMP y la divergencia de los clones de SARM aún no se ha dilucidado. En este estudio, evaluamos el papel que los GMMP pudieron haber desempeñado en la divergencia evolutiva del linaje ST5-SCC mec I del SARM en Latinoamérica. Realizamos una caracterización genómica de 113 aislamientos clínicos de SARM de seis centros de salud latinoamericanos, incluyendo 53 aislamientos recolectados en dos ciudades de Chile (Santiago y Concepción). Encontramos un plásmido (pSCL4752) que alberga genes de resistencia al arsénico, cadmio y mercurio en el 65% ( n = 71) de los aislados ST5-SCC mec I. También observamos una divergencia geográfica asociada a la presencia de pSCL4752 en aislados chilenos, con una mayor frecuencia en aislados de Concepción (88%) en comparación con Santiago (29%). Curiosamente, un análisis de reloj molecular reveló que esta divergencia se produjo tras el terremoto y tsunami de magnitud 8,8 Mw que azotó la zona de Concepción en 2010. Además, nuestros resultados demuestran que la presencia de pSCL4752 puede ser beneficiosa o perjudicial para los aislados ST5-SCC mec I, dependiendo de la disponibilidad ambiental de estos metales pesados. Nuestros resultados sugieren que la divergencia del linaje ST5-SCC mec I MRSA en América Latina podría haber sido fomentada por desastres ambientales e influenciada por la presencia/ausencia de HMRG albergados en un plásmido. IMPORTANCIA El Staphylococcus aureus resistente a la meticilina (MRSA) es una de las principales causas de infecciones potencialmente mortales en todo el mundo y una creciente preocupación para la salud pública. El aumento de bacterias resistentes a los antibióticos, como el MRSA, a menudo está vinculado a adaptaciones genéticas que mejoran su supervivencia. Nuestra investigación arroja luz sobre cómo los cambios ambientales, como los desencadenados por un desastre natural, pueden influir en la evolución y la propagación geográfica de un linaje de MRSA altamente resistente en América Latina. Identificamos un plásmido que porta genes de resistencia al arsénico, cadmio y mercurio, el cual se asoció con la divergencia geográfica del ST5-SCC mec.Se ha identificado un linaje de SARM con diferencias notables en su prevalencia entre las regiones afectadas por un gran terremoto y tsunami. Al vincular los eventos ambientales con la evolución del patógeno, nuestro estudio destaca el papel de las presiones ecológicas en la propagación del SARM. Estos hallazgos subrayan la necesidad de integrar el monitoreo ambiental en las estrategias de salud pública para comprender mejor el desafío global de la resistencia a los antimicrobianos.
Interparental relationships and parental self-efficacy during transition to parenthood
(Universidad del Desarrollo. Facultad de Psicología, 2026) Bennett Escalona, Ana Flavia; Coo, Soledad
Introduction. The transition to parenthood constitutes a critical period demanding substantial individual and family adjustments. Parental self-efficacy—the beliefs parents hold about their capacity to perform the parental role—is a fundamental resource for successful adaptation to parenthood. Interparental relationships, particularly couple satisfaction and coparenting, emerge as key relational contexts for its development. However, evidence on how these processes unfold longitudinally in mothers and fathers during the perinatal period remains limited.
Objective. The study assessed the contribution of interparental relationships during the transition to parenthood on parental self-efficacy at 6 months postpartum, evaluated as a general domain and as developmental stage-specific tasks, in both parents.
Method. Participants were 234 Chilean couples assessed at three time points: third trimester of pregnancy, three months postpartum, and six months postpartum. Measures included couple satisfaction (DAS), coparenting (CRS), general-domain (EEP) and task-specific (KPCS) parental self-efficacy, and depressive symptoms (BDI). Sequential mediation models with multigroup analysis for dyadic data and an Actor-Partner Interdependence Model (APIM) were implemented.
Results. Coparenting at three months predicted parental self-efficacy at six months in both parents, with a stronger effect for fathers on task-specific self-efficacy. Coparenting mediated the relationship between prenatal couple satisfaction and postpartum parental self-efficacy, with gender differences in the magnitude. The APIM revealed significant actor effects from coparenting on parental self-efficacy at six month postpartum for both parents, but no partner effects were found.
Discussion. Findings highlight the role of coparenting as a central mechanism in the association between couple satisfaction and parental self-efficacy. The stronger influence on fathers suggests that, in contexts where mothers are the primary caregivers, coparenting constitutes a particularly relevant pathway for developing paternal self-efficacy. Results underscore the importance of interventions that strengthen family processes as a resource for both parents during the perinatal period and include fathers in perinatal care.
Retrospective study on disparities in time-to-treatment by health insurance system in Chilean breast cancer patients
(2025) Acevedo, Johanna; Ip, Teresa; Maureira, Lea; Sanchez, Cesar; Osorio, Claudia; Carvajal, Claudia; Rafael Araos; Araos Bralic, Rafael Ignacio; Letelier, Hernan; Acevedo, Francisco; Merino, Tomas
Introduction: Breast cancer is the most common malignancy in the Americas, and the second leading cause of cancer death. Disparities in the time to treatment can significantly impact patient outcomes and typically affect lower socioeconomic individuals and/or ethnic minorities. Our study sought to evaluate disparities in time to treatment at three health institutions in Chile according to their type of health insurance (public or private).
Methods: Our study analyzed a database of breast cancer patients diagnosed between 2017 and 2018. Analyses included descriptive statistics and a linear regression model that incorporated clinical and demographic variables. Additionally, using a proportional risks model, we analyzed the association between clinical variables and mortality.
Results: Public health insurance (National Health Fund, FONASA) was associated with longer time-to-treatment and extended treatment times versus private health insurance (Social Security Institutions, ISAPRE; p < 0.0001). As expected, a more advanced stage at diagnosis was associated with lower survival. Our proportional risks model found that age was a predictor of breast cancer mortality in stage II patients. Also, total treatment time significantly increased the risk of breast cancer mortality in stage I patients. Conversely, total treatment time did not affect mortality on stages II or III.
Conclusions: We found significant disparities in the time to treatment of Chilean breast cancer patients using FONASA versus private ISAPRE. FONASA patients experience delays in the initiation of treatment and longer total treatment times compared to their private insurance counterparts. Finally, longer time-to-treatment was associated with more advanced stages and increased mortality.
INTRODUCCIÓN El cáncer de mama es la neoplasia más frecuente y la segunda causa de muerte por cáncer en el continente americano. Diferencias en los tiempos de espera al tratamiento típicamente afectan a individuos de bajo nivel socioeconómico y minorías étnicas, impactando también el pronóstico y la sobrevida. Este estudio evaluó las diferencias en tiempos de espera al tratamiento en relación al tipo de sistema de salud de los pacientes en tres instituciones de salud en Chile. MÉTODOS Se analizó una base de datos de pacientes de cáncer de mama diagnosticados entre 2017 y 2018. El análisis incluyó estadística descriptiva y un modelo de regresión lineal que consideró variables clínico-demográficas. Además la asociación entre variables clínicas y mortalidad se evaluó a través de un análisis de riesgos proporcionales RESULTADOS El sistema público de salud (Fondo Nacional de Salud, FONASA) se asoció a tiempos de espera al tratamiento más largos y tiempos totales de tratamientos más prolongados en comparación con el sistema privado (Instituciones de Salud Previsional, ISAPRES; p < 0,0001). Etapas más avanzadas al diagnóstico se asociaron a menor sobrevida. El modelo de riesgos proporcionales demostró que la edad es un predictor de mortalidad de cáncer de mama en pacientes en etapa II. Además, el tiempo total de tratamiento aumentó significativamente el riesgo de mortalidad por cáncer de mama en pacientes en etapa I. En contraste, el tiempo total de tratamiento no afectó la mortalidad en etapas II ni III. CONCLUSIONES Se encontraron diferencias significativas en el tiempo de espera al tratamiento entre pacientes Chilenas de cáncer de mama usuarias de FONASA e ISAPRES. Las pacientes de FONASA experimentaron demoras en el inicio de sus tratamientos y tiempos totales de tratamiento más prolongados en comparación a usuarias del sistema privado. Por último, tiempos de espera al tratamiento más extensos se asociaron a etapas más avanzadas y mayor mortalidad.
Geospatial Distribution of Food Environments and Their Association with Sociodemographic Factors in Two Mid-Sized Chilean Cities
(2026) Pinheiro Fernandes, Anna Christina; Ayala, Salvador; Quintiliano Scarpelli Dourado, Daiana; Marques, María; Araneda, Jacqueline
Background/objectives: The spatial interaction between obesity, diet-related chronic diseases, premature mortality, food environments, and social determinants of health is a global concern. This study aimed to analyze the spatial distribution of healthy and unhealthy food outlets in two medium-sized cities in southern Chile.
Methods: A cross-sectional observational study was conducted to characterize the food environment in two medium-sized cities in Chile. Food outlets were geolocated and classified as healthy, regular, or unhealthy, and into four food environment categories (institutional outlets, informal markets, formal markets, and restauration) using validated instruments.
Results: Of 1972 identified sites, 1949 were geolocated. Among these, 246 (12.6%) were classified as healthy, 461 (23.7%) as unhealthy, and 1242 (63.7%) as regular. Food environments comprised 1441 stores (73.9%), 366 restauration (18.8%), 136 street food outlets (7.0%), and six institutional food outlets (0.3%). The two lowest socioeconomic quintiles (Q1-Q2) exhibited a lower proportion of healthy food outlets (39.4%). Significant positive spatial autocorrelation was observed for stores, restaurants, and street food outlets (p < 0.005).
Conclusions: Food environments were unequally distributed, with a higher density of healthy food outlets in areas characterized by greater population density and higher socioeconomic status. The observed spatial autocorrelation highlights the need for targeted public health interventions to reduce inequalities in access to healthy foods. These findings provide evidence to support policies aimed at promoting more equitable and healthier food environments in medium-sized cities.
Tasa de egresos hospitalarios de pacientes con estenosis de la válvula aórtica durante el periodo 2021-2024 en Chile
(2026) Poblete, Isidora; Bustamante, Angela; Cid, Jhonn; Rodríguez, Valentina; Garrido, Javiera
Introducción: La estenosis de la válvula aórtica es la valvulopatía más frecuente, asociada a alta morbimortalidad. Ante el envejecimiento poblacional y la limitada información epidemiológica nacional, surge la necesidad de analizar los egresos hospitalarios. Objetivo: Establecer la tasa de egresos hospitalarios por estenosis de la válvula aórtica entre 2021-2024 en Chile. Metodología: Estudio cuantitativo, observacional, descriptivo y de corte transversal. Se analizaron las tasa de egresos hospitalarios por estenosis de la válvula aórtica según sexo, edad y promedio de estadía hospitalaria, incluyendo todos los egresos con diagnóstico CIE-
10 I35.0 a nivel nacional. Los datos se obtuvieron del Departamento de Estadísticas e Información de Salud y del Instituto Nacional de Estadísticas. Se analizó estadística descriptiva en Microsoft Excel. Resultado: Se registraron 8.147 casos, con una tasa de egresos hospitalarios de 11,02 casos por cada 100.000 habitantes y tendencia al alza. Destaca un predominio en hombres (12,98 casos/100.000 habitantes) y en mayores de 80 años (71,67 casos/100.000 habitantes). El promedio de estadía hospitalaria fue de 11,12 días, con 11,42 para hombres y 10,72 para mujeres. Discusión: El aumento de la tasa de egresos hospitalarios es consistente con el envejecimiento poblacional. Las diferencias por sexo podrían relacionarse con variaciones en la progresión o acceso al diagnóstico. La disminución de la estadía desde 2022 sugiere una recuperación del sistema de salud tras la pandemia. Conclusión: La creciente carga hospitalaria de la estenosis de la válvula aórtica en Chile evidencia la necesidad de planificación sanitaria, con énfasis en factores clínicos y brechas de género.
Introduction: Aortic valve stenosis is the most common valvular heart disease, associated with high morbidity and mortality. Given the aging population and limited national epidemiological data, there is a need to analyze hospital discharges. Objective: To establish the hospital discharge rate for aortic valve stenosis in Chile during 2021-2024. Methodology: Quantitative, observational, descriptive, cross-sectional study. Hospital discharge rate for aortic valve stenosis were analyzed by sex, age, and average length of hospital stay, including all discharges with an ICD-10 I35.0 diagnosis nationwide. Data came from the Department of Health Statistics and Information and the National Institute of Statistics and were analyzed with descriptive statistics in Microsoft Excel. Result:
8.147 cases were recorded, with an hospital discharge rate of 11,02 per 100.000 inhabitants and an upward trend, with predominance in men (12,98/100.000) and in those over 80 (71,67/100.000). Average length of stay was 11,12 days: 11,42 for men and 10,72 for women. Discussion: The hospital discharge rate increase is consistent with population aging; sex differences may reflect variations in progression or access to diagnosis; the shorter stay
since 2022 suggests health-system recovery after the pandemic. Conclusion: The growing hospital burden of aortic valve stenosis in Chile highlights the need for healthcare planning, emphasizing clinical factors and gender gaps.
Comparison of two techniques for measuring Demodex folliculorum and Demodex brevis in rosacea patients: standardized skin surface biopsy vs. direct microscopic examination
(2025) Pérez Wilson, Jaime; Andreani Figueroa, Sebastián; Aspillaga Vergara, Soledad; Benedetto Eblen, Juana; Lecaros Cornejo, Cristóbal; García Ramos, Viviana; Méndez Villanueva, Diego; Velásquez Muñoz, Daniel; Ríos, Paulina; Di Gennaro, Angelo; Olivares, Tomás; Olivares, Jorge
Rosacea is a chronic inflammatory skin disease affecting approximately 5.4% of the world population. Among its pathogenic factors is infestation by Demodex spp. Standardized skin surface biopsy (SSSB) and direct microscopic examination (DME) are widely used methods to measure Demodex spp density (Dd); however, there is no agreement on the method of choice, nor the prevalence of infestation in rosacea patients. This study compared both techniques in rosacea patients. A prospective study was conducted with 61 patients diagnosed with rosacea by dermatologists from two dermatology centres. Dd was evaluated using SSSB and DME in each patient. Results, median sampling time and reported pain were analyzed using appropriate statistical methods. The median Dd was significantly higher with SSSB (11 mites/cm2) compared to DME (1 mites/cm2; P < 0.001). Infestation (>5 mites/cm2) was detected in 64% of patients with SSSB and in 28% with DME (P < 0.001). The median sampling time was longer for SSSB (60 s) than for DME (30 s; P < 0.001). Both methods were associated with mild pain, slightly lower with DME (P = 0.033). SSSB proved more effective than DME for detecting Demodex spp. in rosacea, identifying a greater total number of mites and a higher percentage
of infestation. Up to 64% of rosacea patients showed infestation with Demodex spp. using the SSSB technique. The results reinforce the use of SSSB as the standard technique for diagnosing Demodex spp. infestation in rosacea patients.
Connexin46 in the nucleus of cancer cells: a possible role as transcription modulator
(2025) Fernández, Ainoa; Orellana, Viviana; Llanquinao, Jesús; Nuñez, Gonzalo; Perez Moreno, Pablo; Contreras, Sebastián; Martin, Alberto; Mammano, Fabio; Alfaro, Ivan; Calderón, Juan; Stehberg, Jimmy; Sáez, Mauricio; Retamal, Mauricio A.
Background: Oncogenes drive cancer progression, but few are active exclusively in tumor cells. Connexins (Cxs), traditionally recognized as ion channel proteins, can localize to the nucleus and regulate gene expression, playing key roles in both physiological and pathological processes. Cx46, once thought to be restricted to the eye lens, has been implicated in tumor growth, though its underlying mechanisms remain unclear. This study investigates the nuclear presence of Cx46 in cancer cells and its potential role as a transcriptional modulator.
Methods: We employed ChIP-Seq, confocal immunofluorescence, and nuclear protein purification to assess Cx46 localization and DNA interactions. Functional assays were conducted to evaluate its effects on invasion, division, spheroid formation, and mesenchymal marker expression. Single-point mutations and molecular dynamics simulations were used to explore potential Cx46-DNA interactions.
Results: Cx46 mRNA upregulation was found in a variety of tumors compared to adjacent healthy tissue. In HeLa cells, which do not express Cx46, its transfection promoted proliferation, invasion and self-renewal capacity, cancer stem cell traits and mesenchymal features. Consistently, in Sk-Mel-2, which naturally express Cx46, reduced Cx46 expression led to a decrease in the similar parameters. In HeLa cells, nuclear Cx46 was detected in two forms, full length 46 kDa and a 30 kDa fragment (GJA3-30 k), ChIP-Seq experiments revealed that Cx46 binds to the DNA at intergenic and promoter regions, leading to the activation of oncogenic pathways. Molecular dynamics simulations suggest that GJA3-30 k dimerizes in a RAD50-like structure, forming stable DNA complexes. Cx46 and in some cases GJA3-30 k were detected in the nuclei of multiple cancer cell lines, including prostate, breast and skin cancers.
Conclusions: Our findings reveal a novel nuclear role for Cx46 in cancer, demonstrating its function as a transcriptional regulator and its potential as a therapeutic target.
Paw Skin as a Translational Model for Investigating Fibrotic and Inflammatory Wound Healing Defects in Recessive Dystrophic Epidermolysis Bullosa
(2025) De Gregorio, Cristian; Ramos, Giselle; Morales, Bernardo; Ezquer, Fernando; Marcelo Ezquer; Ezquer, Marcelo
Recessive dystrophic epidermolysis bullosa (RDEB) is a severe genetic disease caused by COL7A1 mutations. It leads to skin fragility, chronic inflammation, and impaired wound healing. The condition often results in fibrotic scarring, pseudosyndactyly, and cutaneous squamous cell carcinoma (SCC). However, current animal models fail to fully replicate chronic RDEB wounds. In this study, we used Collagen VII-hypomorphic mice (Col7a1flNeo/flNeo) and created full-thickness wounds on their paw skin, an area prone to fibrosis due to mechanical stress. We analyzed the healing process using histology, immunofluorescence, and electron microscopy. The RDEB mice showed delayed wound closure, increased inflammation, and poor granulation tissue formation. At 30 days post-injury, we observed persistent fibrosis, with elevated levels of Collagen I, α-SMA+ myofibroblasts, and tenascin-C. These mice also had fewer intraepidermal nerve fibers, which may help explain the neuropathic pain associated with RDEB. Our model reproduces the main features of chronic RDEB wounds. It offers a useful tool for evaluating therapies aimed at reducing inflammation, fibrosis, and tumor risk in these patients.
Nivel de conocimiento y percepción de sexualidad saludable en personas mayores autovalentes: estudio descriptivo en chillán, chile
(2025) Pérez, Giselle; Pérez, Cristina; Sandoval, Carla; Sepúlveda, Fernanda; Vásquez, Melanie; Rojas, Patricia; Mora, Guillermina
Introducción: Las preocupaciones propias de los cambios a consecuencia de la edad, dejan de lado algunos factores asociados a la salud. Objetivo: Describir las características sociodemográficas, socioculturales y el nivel de conocimiento de sexualidad saludable en personas mayores autovalentes que asisten al programa Más Adultos Mayores Autovalentes, de cuatro Centros de Salud Familiar de la Ciudad de Chillán. Metodología: Se realizó un estudio con enfoque cuantitativo, observacional descriptivo. La población estuvo constituida por 779 personas mayores de 60 años inscritas en el programa. Se calculó una muestra no probabilística por conveniencia con una confiabilidad del 85% y un error estándar del 5%. Se logró recolectar 155 respuestas. Se construyó un
instrumento de respuesta cerrada, sometido a validación mediante juicio de expertos, quedando conformado por 26 preguntas. La recolección de datos se realizó en forma presencial. El estudio contó con el permiso del Comité Ético Científico del Hospital Herminda Martin de Chillán, CEC-HCHM N°806636/2024. Resultado: El 81% de las personas mayores no tienen conocimientos sobre sexualidad saludable, el 94% tiene una percepción negativa sobre la sexualidad saludable, el 13% no puede hablar libremente sobre su sexualidad, ya que a su entorno familiar le molesta y el 46 % de las personas mayores encuestadas se siente juzgado por tener una vida sexual activa. Conclusiones: El estudio evidenció bajo conocimiento de sexualidad saludable en personas mayores lo
que sugiere fortalecer la educación sexual respecto de factores protectores y de riesgo que permitan al individuo desarrollarse en todos los aspectos de la vida.
Introduction: The concerns of age-related changes, leaving aside some factors associated with health, this study aims to the level of knowledge about healthy sexuality in self-reliant seniors attending the More Self-sufficient Senior program at four Family Health Centers in the City of Chillán, 2024. Methodology: A quantitative, observational descriptive study was conducted. The population consists of 779 elderly persons over 60 years enrolled in the program. A non-probabilistic sample is calculated for convenience with a reliability of 85% and a standard error of 5%. 155 responses were collected. For the data collection, a closed response instrument was built, based on objective and updated literature review, which was submitted to validation using the expert judgment methodology, consisting of 26 questions. The data collection was carried out in person. The study has the permission of the Scientific Ethics Committee of the Hospital Herminda Martin de Chillán, which granted the study authorization CEC-HCHM N°806636/2024. Result: Of the total respondents, 81% of older people have no knowledge about healthy sexuality, 94% have a negative perception about healthy sexuality, 13% cannot speak freely about their sexuality because it bothers their family environment and 46% of older people surveyed feel judged for having an active sex life. Conclusions: The study revealed a low level of knowledge about healthy sexuality among older adults, suggesting the need to strengthen sexual education regarding protective and risk factors that allow individuals to develop in all aspects of life.
TGFβ links EBV to multisystem inflammatory syndrome in children
(2025) Goetzke, Carl; Massou, Mona; Frischbutt, Stefan; Guerra, Gabriela; Ferreira, Marta; Heinrich, Frederik; Von Stuckra, Anne; Wisniewsk, Sebastian; Lich, Jan; Bondarev, Marina; Ehler, Lisa; Khaldi, Samira; Javouhe, Etienne; Pons, Sylvie; Trouillet, Sophie; Ozsurek, Yasemin; Zhang, Yu; Poli Harlowe, María Cecilia; Discepolo, Valentina; Lo Vecchio, Andrea; Sahin, Bengü; Verboom, Murielle; Hallenslebe, Michael; Heuhse, Anja; Astudillo, Camila; Espinosa, Yazmin; Vial, Maria Cecilia; Dobbs, Kerry; Delmont, Ottavia; Montealegre, Gina; Magliocco, Mary; Barron, Karyl; Danielson, Jeffrey; Petrov, Lev; Unterwalder, Nadine; Sawitzk,i Birgit; Matz, Mareen; Lehmann, Katrin; Gratop, Alexander; Von Bernuth, Horst; Burkhardt, Lisa; Wiese, Niklas; Peter, Lena; Schmueck, Michael; Amini, Leila; Maurer, Marcus; Roehmel, Jobst; Gewur, Benjamin; Yonker, Lael; Witkowsk, Mario; Kruglov, Andrey; Mall, Marcus; Su, Helen; Ozen, Seza; Radbruch, Andreas; Belot, Alexandre; Durek, Pawel; Kallinich, Tilmann; Mashregh, Mir-Farzin
In a subset of children and adolescents, SARS-CoV-2 infection induces a severe acute hyperinflammatory shock1 termed multisystem inflammatory syndrome in children (MIS-C) at four to eight weeks after infection. MIS-C is characterized by a specific T cell expansion2 and systemic hyperinflammation3. 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. 4,5). 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.