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The proportion of genetic similarity for liability for neuroticism in mother-child and mother-father dyads is associated with reported relationship quality
(2025) Pearson, Rebecca; Braithwaite, Elizabeth; Cadman, Tim; Culpin, Iryna; Costantini, Ilaria; Cordero, Miguel; Bornstein, Marc; James, Deborah; Kwong, Alex; Jones, Hannah; Sallis, Hannah
This study aims to explore the influence of genetic similarity for neuroticism liability in mother's reported quality of relationship with her child and partner. Such understanding could provide insight into the role of genetic similarity in neuroticism liability in close relationships. Molecular genetic data in 4,704 mothers, partners, and children in the Avon Longitudinal Study Parents And Children (ALSPAC) study were used to derive the proportion of genetic similarity in neuroticism liability between mother and child, and mother and partner, for genetic variants associated with neuroticism. Associations between genetic similarity in neuroticism liability scores and mothers' reported enjoyment and conflict in the parenting relationship (child ages 0-3) and her reported partner relationship were examined. For a one standard deviation (SD) increase in similarity in mother and child genetic variants associated with neuroticism, there was a 0.15SD (95%CI = 0.003 to 0.500, p = 0.046) increase in maternal reported enjoyment in their relationship. This association was greater where mother and child were both in the top quartile for high neuroticism (standardised beta = 0.29, 95%CI = 0.02 to 0.56, p = 0.034). Similar patterns of results emerged for similarity for genetic variants associated with neuroticism between mothers and partners, and the quality of the mother-partner relationship. These results highlight how phenotypic variation (i.e. the link between PGS scores and mothers reported enjoyment) linked to genetic liability in one individual may be linked with the genetic liability of those around them (i.e. the genetic liability of the infant). In other words, parenting and intimate partner relationships as perceived by the mother were explained not by one or the other's genetic score, but by the similarity between them These exploratory findings present an intriguing mechanism by which similarity between genetic liability might be linked to family relationships.
Programas after school y su relación con la inserción laboral femenina: un estudio comparativo en establecimientos de la Fundación Acompañando Pasos, zona central de Chile
(Universidad del Desarrollo. Facultad de Gobierno, 2026) Merino, Bernardita; Rojas, Armando; Bilbao, Gilda
El presente estudio analiza la relación entre la participación en programas after school y la inserción laboral de mujeres con hijos e hijas en edad escolar, a partir de un diseño cuantitativo, no experimental, transversal y comparativo.
No evidence for exosome treatment in reducing alcohol relapse – a failed confirmatory multi-center study
(2025) Meinhardt, Marcus; Habelt, Bettina; Skorodumov, Ivan; Schwarz, Cindy; Bernhardt, Nadine; Winter, Christine; Hardar, Ravit; Müller, Christian; Israel, Yedy; Ezquer, Fernando; Spanagel, Rainer
Preclinical studies have suggested that intranasal administration of mesenchymal stem cell-derived exosomes can reduce alcohol intake and relapse-like behavior in rodents. To assess the translational potential of these findings, we conducted a preregistered, multi-center preclinical randomized controlled trial (preRCT) across several German research sites. Using the alcohol deprivation effect (ADE) model in both male and female Wistar rats, we evaluated whether exosome treatment attenuates relapse-like drinking behavior following repeated deprivation phases. Given the hurdles in standardizing exosome isolation, dosage, and intranasal delivery into the brain, we performed first a functional validation experiment of intranasally delivered exosomes. For providing such a functional proof, we conducted electrocorticography (ECoG) recording and showed that exosomes are capable of mitigating impaired electrophysiological activity in the prefrontal cortex in rats that underwent the ADE procedure. However, contrary to previously published positive findings, our confirmatory multi-site preRCT results did not demonstrate a significant reduction in ethanol consumption during an ADE in Wistar rats following exosome treatment. No sex or site-specific effects were observed. Given the absence of efficacy, the study was terminated early in alignment with the 3R principles of animal research ethics. These findings suggest that the previously reported benefits of exosome treatment may be model-specific and do not generalize to a broader genetic background or experimental model. Our results emphasize the necessity of replication across diverse preclinical models and rat lines prior to clinical translation and highlight the importance of publishing null results to improve transparency and reproducibility in addiction research.
Characterization of Hydrogel Beads for the Gradual Release of Origanum vulgare L. Essential Oil and Evaluation of Their Antifungal Activity Against Candida albicans
(2025) Concha, Victoria; Díaz, Mario; Duarte, Luisa; Jara, José; Molina, Alfredo
Candida albicans infections are associated with high morbidity and mortality worldwide. Current antifungal therapies are limited by adverse effects and the emergence of resistant strains, which compromise long-term efficacy. Previous studies have shown that Origanum vulgare L. essential oil (OvEO) possesses strong antifungal activity; however, its volatility and physicochemical instability hinder clinical application. The aim of this study was to encapsulate OvEO in a hydrogel and evaluate its release kinetics, chemical composition, structural properties, and antifungal activity. We assessed its release kinetics, chemical composition, structural characteristics (FTIR; SEM), and antifungal activity against C. albicans. OvEO was successfully encapsulated into hydrogel beads, enabling a gradual release profile, with in vitro release of phenolic compounds reaching 100% at 48 min. SEM revealed an irregular surface with small pores and crystalline aggregates distributed across the bead surface. OvEO-loaded hydrogel beads inhibited C. albicans growth with an IC50 of 0.15 ± 0.05 mg/L for strain 90029 and 0.2 ± 0.06 mg/L for strain 10231. At these concentrations, adhesion to abiotic surfaces was reduced by 60–80%. These findings support the potential of OvEO-loaded hydrogel beads as an alternative approach for the treatment of fungal infections, offering a complementary strategy to current antifungal agents.
Polygenic scores contribution to Parkinson's disease comorbidities
(2025) Hernández, Carlos; Villaman, Camilo; Tejos, Cristian; Repetto, Gabriela; Leu, Costin; Lal, Dennis; Mata, Ignacio; Klein, Andrés; Pérez Palma, Eduardo
Comorbidities are common in Parkinson's disease and significantly impact the disease progression and management. While polygenic scores have been widely used to assess genetic risk for complex diseases, their role in comorbidity presentation in Parkinson's disease remains unclear. This study investigates whether genetic predisposition to comorbidities, as measured by polygenic scores, differs between individuals with Parkinson's disease and the general population and explores how genetic risk influences disease onset and sex-related differences. We analysed data from 4144 individuals with Parkinson's disease and 370 480 individuals from the general population in the UK Biobank, focusing on four comorbidities with high-quality genome-wide association study data: Type 2 diabetes, major depressive disorder, migraine headaches and epilepsy. We first compared polygenic score distributions between individuals with Parkinson's disease and the general population. While our findings indicate that comorbidities and polygenic risk scores do not significantly differ between individuals with Parkinson's disease and the general population, we show an association with disease onset and sex-specific differences. Individuals with earlier disease onset (50-70 years old) had higher genetic risk for major depressive disorder (odds ratio: 2.19, P-value: 1.27 × 10⁻¹⁵) and epilepsy (odds ratio: 1.58, P-value: 0.00845). Additionally, a female participant with Parkinson's disease exhibited higher genetic risk scores for major depressive disorder (odds ratio: 1.5, P-value: 0.0119) and migraine headaches (odds ratio: 2.1, P-value: 0.0155), while a male participant displayed higher genetic risk scores for Type 2 diabetes (odds ratio: 2.7, P-value: 2.11 × 10⁻¹⁷). Comorbidity-polygenic score did not differ between people with versus without Parkinson's disease, yet within Parkinson's disease, a higher genetic burden for specific comorbidities was linked to earlier onset and sex-specific presentation, implicating common variants as modifiers of clinical heterogeneity rather than the primary disease risk. These results enhance our understanding of the genetic influences shaping the broader clinical presentation of Parkinson's disease and highlight the need for further research into the interplay between genetic risk factors, comorbidities and disease heterogeneity.
Therapeutic Effects of Intranasal Administration of Mesenchymal Stem Cell-Derived Secretome in Rats Exposed to Chronic Unpredictable Mild Stress
(2025) Ávila, Alba; Riveros, María; Adasme, Sofía; Guevara, Coram; Del Rio, Rodrigo; Ortiz, Fernando; Leibold, Nicole; Ezquer, Fernando
Background: Major depression is a significant source of suffering and economic loss. Despite efforts to understand this condition and find better treatments, the burden imposed by this disease continues to rise. Most approved pharmacological treatments for depression focus on controlling the availability of monoamines in synapses. However, accumulating evidence suggests that neuroinflammation, oxidative stress, and reduced hippocampal neurogenesis play key roles as causal factors in the development of major depression symptoms. Therefore, preclinical testing of pharmacological approaches targeting these factors is essential. Mesenchymal stem cells (MSCs) are known for their potential as powerful antioxidants and anti-inflammatory agents, exerting neuroprotective actions in the brain. They produce various therapeutic molecules in a paracrine manner, collectively known as secretome. Methods: In this work, we evaluated the antidepressant potential of repeated intranasal administration of MSC-derived secretome in an animal model of major depressive disorder induced by chronic mild unpredictable stress. Results: We observed that intranasal administration of MSC-derived secretome reduced the appearance of some of the behavioral parameters commonly associated with major depression, including anhedonic, apathetic, and anxious behaviors, inducing a strong reduction in the overall depression score compared to vehicle-treated animals. At the structural level, secretome administration prevented increased astrocyte density and the atrophy of astrocyte processes observed in vehicle-treated stressed animals. Additionally, secretome administration induced an increase in myelin levels and oligodendroglia in the cortex. Conclusions: Our data suggests that intranasal administration of MSC-derived secretome may represent a potential therapeutic alternative to current treatments for this devastating pathology.
Ultra-Processed Foods and Markers of Systemic Inflammation in Children
(2026) Awad, Camila; Rubilar, Paola; Hirmas Adauy, Macarena; Iglesias, Verónica; Muñoz, María; Retamal, Mauricio A.; Carvajal, Cristóbal; Dadvand, Payam; Lassale, Camille
Diets high in ultra-processed foods (UPF) have been associated with negative health outcomes in adults; however, UPF's impact on children's health and their underlying mechanisms remain underexplored, despite the rising prevalence of their intake in younger populations. We aimed to investigate the association between UPF intake and systemic inflammation in primary school children. This study included 450 children aged 7–10 years participating in a birth cohort in Arica, Chile (2023). Using the NOVA food classification system, we calculated the intake of UPF (expressed in %kcal) from a 44-item food frequency questionnaire (FFQ). The associations between UPF intake (exposure) and an array of cytokine levels (IL-6, IL-8, IL-10, IL-12, IL1β, TNF-α) were assessed using multiple linear regression models, adjusted for relevant covariates. The mean (SD) UPF intake was 29% (10.5%) of the total energy intake. Some of the associations appeared non-linear; therefore, participants were grouped into tertiles of UPF intake. In adjusted models, a suggestive trend across tertiles was observed for IL-1β (trend p-value 0.01). Stratified analyses by age suggested an association between UPF intake and IL-6 in older children (≥9 years) only (p-value for interaction=0.02). We found potential associations between UPF intake and cytokine levels in school-aged children. These results may suggest inflammation as a mechanism underlying the adverse health consequences of UPF consumption in children.
Cost-effectiveness of strategies using preventive interventions to protect infants in Chile from respiratory syncytial virus
(2025) Bolanos, Rafael; Araos Bralic, Rafael Ignacio; Gonzalez, Cecilia; Sepulveda, Dino; Falconi, Juan; Averin, Ahuva; Atwood, Mark; Quinn, Erin; Law, Amy; Mendes, Diana
Background: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract illness (LRTI; RSV-LRTI) among infants in Chile; young infants and infants born prematurely are at greatest risk.
Research design and methods: A cohort model was developed to evaluate cost-effectiveness of strategies preventing RSV-LRTI in infants. Using the model, we calculated the economically justifiable price (EJP) of maternal RSVpreF vaccination (MV) versus no intervention and then evaluated the cost-effectiveness of MV (cost/dose assumed at EJP) with complementary use of monoclonal antibody nirsevimab for unprotected infants (MV+N) versus nirsevimab alone (NA) to prevent RSV-LRTI. Nirsevimab published price was $260.00; costs/prices reported in 2023 US$.
Results: NA yielded 20,247 cases (hospital: 3,773, emergency ward: 16,474) and $57.2 million (M) in total costs (medical: $6.3 M, intervention: $48.7 M, indirect: $2.2 M). MV+N yielded 23,906 cases (hospital: 3,137, emergency ward: 20,769) and $28.7 M in costs (medical: $4.8 M, intervention: $21.7 M [RSVpreF assumed $75.77/dose; nirsevimab procured $260.00/dose], indirect: $2.2 M). With costs lower by $28.4 M and increased quality-adjusted life-years, MV+N would be cost-saving versus NA.
Conclusions: RSVpreF vaccination among pregnant women along with nirsevimab for unprotected infants in Chile would be the most efficient use of resources, yielding substantial cost savings compared to use of nirsevimab alone.
Trial registration: ClinicalTrials.gov NCT04424316 NCT03979313.
Genetics services in Latin America: a descriptive study of availability and utilization of genetics in healthcare
(2025) German, Ryan; Atkinson, Erin; Storch, Eric; Soler, Claudia; Margarit, Sonia; Lupo, Philip; Pereira, Stacey
Genetic services are expanding globally, but access remains limited in low-resource regions such as Latin America. Understanding current service availability, barriers, and facilitators is critical to guide capacity building and improve patient care. We conducted a cross-sectional survey of healthcare professionals providing genetic services in Latin America. The survey, available in Spanish and English, assessed genetic services, referral patterns, testing availability, barriers, facilitators, and perceived needs. Descriptive statistics summarized quantitative data, and thematic analysis was applied to openended responses. Eighty-five respondents from 18 countries reported broad clinical activity across pediatric, cancer, and adult-onset genetic conditions. Commonly ordered tests included karyotype, gene panels, and exome sequencing, with many sending samples abroad. Key barriers included high costs, workforce shortages, and limited clinician familiarity with testing. Facilitators included clinician interest and laboratory partnerships. Respondents emphasized the need for expanded test access, workforce development, and increased training opportunities. Genetic services in Latin America show substantial growth but face persistent barriers. Strengthening local infrastructure, training, and collaborative efforts is essential to improve access, reduce diagnostic delays, and enhance patient outcomes.
Biofilm formation on collagen substrates modulates Streptococcus mutans bacterial extracellular nanovesicle production and cargo
(2025) Leiva, Camila; Berríos, Pablo; Saavedra, Paula; Carrasco, Javiera; González, José; Vera, Mario; Tarifeño, Estefanía; Schuh, Christina; Aguayo, Sebastian
Streptococcus mutans is the major microbial etiological agent of dental caries and can adhere to surfaces such as type-I collagen, which is present in dentin and periodontal tissues. Recent studies have characterized planktonic S. mutans bacterial extracellular vesicles (bEVs) at the nanoscale range and demonstrated environmental-induced changes due to sugar presence or pH alterations. However, to date, no studies have explored whether surface-derived changes can modulate bEV production in the context of oral biofilm formation in the elderly. Therefore, this work aimed to determine the role of biofilm formation and collagen glycation on the nanoscale morphology and proteomic composition of S. mutans bEVs. For this, bEVs from S. mutans biofilms on native and glycated collagen surfaces were isolated, characterized, and compared to bEVs from planktonic cells. Nanoparticle tracking analysis (NTA), atomic force microscopy (AFM), and electron microscopy confirmed bEV production and showed that bEVs from biofilms are smaller in size and less abundant than those from planktonic cells. Furthermore, proteome analysis revealed that S. mutans biofilm formation on native and glycated collagen led to the enrichment of several key virulence proteins. Also, a shift towards proteins involved in metabolic processes was found in bEVs following biofilm formation on collagen surfaces, whereas glucan metabolism proteins were overexpressed in vesicles from the planktonic state. These results demonstrate that biofilm formation, as well as the glycation of collagen associated with aging and hyperglycaemia, can modulate bEV characteristics and cargo and could play a central role in S. mutans virulence and the development of diseases such as dental caries and periodontal disease.
Incontinencia fecal femenina: una condición silenciada en el discurso de salud pélvica
(2026) Cárdenas, Valentina; Soto, Javiera; Comicheo, Nelly; Paredes, Natalia; Ñanco, Lisset; Rojas, Daniela; Hernández, Alejandro
La incontinencia fecal es una disfunción de suelo pélvico que ha permanecido invisibilizada en el ámbito clínico y científico a pesar de que la salud pélvica femenina se ha tratado históricamente desde una perspectiva predominantemente fisiopatológica, lo que ha limitado la comprensión integral de sus implicancias biopsicosociales. Esta condición, a menudo silenciada debido al estigma, la falta de información y la vergüenza, presenta un impacto considerable en la calidad de vida de las mujeres. La incontinencia fecal, además de su dimensión clínica, tiene un fuerte impacto a nivel psicosocial, afectando la autopercepción, la salud mental, las relaciones interpersonales y la vida social. Este artículo reflexivo tiene por objetivo sugerir una perspectiva integral que conecte lo fisiológico con lo psicosocial, enfatizando la importancia de visibilizar este problema en la conversación sanitaria y fomentar un cuidado empático e interdisciplinario.
Fecal incontinence is a pelvic floor dysfunction that has remained invisible in the clinical and scientific fields, despite the fact that female pelvic health has historically been treated from a predominantly pathophysiological perspective, which has limited the comprehensive understanding of its biopsychosocial implications. This condition, often silenced due to stigma, lack of information, and shame, has a considerable impact on women's quality of life. Fecal incontinence, in addition to its clinical dimension, has a strong psychosocial impact, affecting self-perception, mental health, interpersonal relationships, and social life. Thisreflective article aims to suggests a comprehensive perspective that connects the physiological with the psychosocial, emphasizing the importance of making this problem visible in healthcare conversations and fostering empathetic and interdisciplinary care.
Estrategias para aumentar la autoeficacia frente al dolor en pacientes con dolor musculoesquelético cróActividad de Grado presentada a la Facultad de Medicina de la Universidad del Desarrollo para optar al grado académico de Magíster en Terapia Física y Rehabilitación (MAKI)nico de hombro: Scoping review
(Universidad del Desarrollo. Facultad de Medicina, 2026) Fuentes Werlinger, Nicolas; Araya Castro, Paulina
Antecedentes/Objetivo: El dolor musculoesquelético crónico de hombro persiste más de seis meses en aproximadamente el 50% de los casos, afectando significativamente la funcionalidad, el trabajo y la calidad de vida. La autoeficacia frente al dolor es considerada el mediador psicológico más potente de la discapacidad y la respuesta al tratamiento en poblaciones con dolor crónico. Sin embargo, la evidencia que describe estrategias para mejorar la autoeficacia frente al dolor específicamente en personas con dolor crónico de hombro es limitada. Este scoping review tuvo como objetivo mapear y describir las estrategias dirigidas a aumentar la autoeficacia frente al dolor en personas con dolor musculoesquelético crónico de hombro.
Métodos: Se realizó un scoping review siguiendo las directrices del Joanna Briggs Institute (JBI), reportado según la declaración PRISMA-ScR. Se realizó una búsqueda en cuatro bases de datos (PubMed, EBSCOhost, SciELO y Science Direct). Dos revisores independientes seleccionaron los estudios aplicando criterios de elegibilidad predefinidos, con discrepancias resueltas por un tercer revisor. Los diseños elegibles incluyeron ensayos clínicos aleatorizados, estudios cuasiexperimentales, de cohorte y series de casos.
Resultados: Se identificaron 4603 registros; tras eliminar 406 duplicados y evaluar 109 textos completos, se incluyeron 4 estudios que abarcaron desde 2011 hasta 2022, con 492 participantes. Las estrategias fueron clasificadas como multicomponentes o de terapia física, todos los estudios utilizaron el PSEQ como medida de autoeficacia frente al dolor. Las estrategias multicomponentes mostraron mejoras significativas en autoeficacia frente al dolor junto a cambios en múltiples variables psicológicas. El entrenamiento neuromuscular supervisado también mejoró significativamente la autoeficacia frente al dolor, mientras que un programa domiciliario no supervisado no mostró cambios en esta variable.
Conclusión: La evidencia disponible sobre estrategias para mejorar la autoeficacia frente al dolor en personas con dolor crónico de hombro sigue siendo escasa y se encuentra en una etapa inicial. Los hallazgos sugieren que las intervenciones supervisadas en formato grupal, especialmente las multicomponentes, se asocian a mejores resultados.
Capture and detection of extracellular vesicles derived from human breast cancer cells using a 3D self-assembled nanostructured SiO2 microfluidic chip
(2025) Cabeza, Carolina; Rojas, Felipe; Lobos, Lorena; Lemaitre, Dominique; Villena, Juan; Cordero, María; Hassan, Natalia; Ortiz, Rina
Background: Tumor-derived extracellular vesicles offer a minimally invasive approach to evaluate tumor progression and metastasis. However, detecting biomarkers, such as extracellular vesicles in body fluids during the early stages of disease, remains a significant challenge. Conventional methods like ultracentrifugation-based isolation or Western blot protein quantification are time-consuming, require large sample volumes, and offer low yield and sensitivity. Therefore, the development of new biosensors for the specific and efficient analysis of tumor extracellular vesicles is urgently needed.
Methods: Microfluidic devices provide extraordinary benefits for bioanalysis, offering a large surface area for the contact between target molecules and the biosensor, significantly enhancing the specificity, efficiency, and speed. These devices also enable nanoscale and microscale work using reduced sample volumes. In this study, we developed a three-dimensional self-assembled SiO2-based nanostructured microfluidic chip, bioconjugated with specific antibodies targeting exosomal markers for the selective capture of CD63- and CD81-positive extracellular vesicles from breast cancer-derived conditioned cell culture media.
Results: The three-dimensional SiO2-based microfluidic chip effectively captured extracellular vesicles expressing CD63 and CD81 antigens from breast cancer cell culture media. This evidence demonstrates the potential of this platform to detect extracellular vesicles as biomarkers for cancer, providing a specific and efficient, non-invasive approach for cancer diagnostics.
Conclusions: This study highlights the potential application of three-dimensional SiO2-based microfluidic chips for detecting extracellular vesicles as a non-invasive liquid biopsy tool for breast cancer. The findings show a specific and efficient device as an alternative to conventional biomarker detection techniques.
Surgical outcomes from haematoma evacuation for intracerebral haemorrhage in the INTERACT3 study
(2025) Hu, Xin; Ouyang, Menglu; Xu, Jianguo; Liu, Yi; Li, Xi; Jiang, Yan; Chen, Xiaoying; Billot, Laurent; Qiang, Li; Malavera, Alejandra; Munoz Venturelli, Paula; Thang, Nguyen; Wahab, Kolawole; Pandian, Jeyaraj; Wasay, Mohammad; Pontes-Neto, Octavio; Abanto, Carlos; Arau, Antonio; Li, Zongping; Chen, Minhui; Wang, Xiaofeng; Yang, Chengyi; Xin, Xiaodong; Jiang, Dehua; Zheng, Jun; Yu, Zhiyuan; Xiao, Anqi; Tao, Chuanyuan; Chen, Lei; Wu, Bo; Li, Hao; Anderson, Craig; You, Chao; Song, Lili; Ma, Lu; INTERACT3 Investigators
Background: There is ongoing controversy as to whether surgical intervention to haematoma evacuation benefits patients with acute intracerebral haemorrhage (ICH). This study aimed to evaluate the association of surgical intervention to evacuate the haematoma and 6-month functional outcome in participants of the third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT3).
Methods: This was a secondary analysis of INTERACT3, which enrolled adults (age ≥18 years) spontaneous ICH patients within 6 h after onset. INTERACT3 was an international, multicentre, prospective, stepped-wedge, cluster randomised, blinded outcome assessed, clinical trial undertaken at 121 hospitals in 10 countries between December 12, 2017 and December 31, 2021. To limit heterogeneity in the results, we restricted analyses to participants in China. The primary outcome was poor functional outcome, defined by a score of 5-6 on the modified Rankin scale (mRS), at 6 months. Secondary outcomes include a mRS score of 4-6 and mortality at 6 months. Sensitivity analysis included propensity score matched analysis and the imputation of missing outcome variables. The effect of timing on surgical outcome was also evaluated. The INTERACT3 trial was registered at ClinicalTrials.gov (NCT03209258) and CHiCTR.org.cn (ChiCTR-IOC-17011787).
Findings: Of 5772 participants (mean age 62.0 ± 12.5 years) at 82 sites in China, 1411 (24.4%) received surgery in which craniotomy (72.6%) was the most common approach. After adjustment for confounding variables, surgery to evacuate the haematoma was associated with lower odds of a poor functional outcome (odds ratio 0.71, 95% CI 0.55-0.92; p = 0.010) and mortality (odds ratio 0.55, 95% CI 0.40-0.75; p = 0.0001) at 6 months. The association was consistent in propensity score matching analysis and sensitivity analysis by imputation. We did not detect significant differences in outcome between those who received surgery on the same day of hospital arrival compared to those who received surgery on the second or later days. In analysis limited to participants with supratentorial ICH and with a haematoma volume 30 mL or more, evacuation of the haematoma was associated with lower odds of poor functional outcome (n = 1234, odds ratio 0.68, 95% CI 0.46-0.99; p = 0.042) and mortality (n = 1291, OR 0.45, 95% CI 0.29-0.69; p = 0.0003).
Interpretation: This secondary analysis of the INTERACT3 indicates that evacuation of the haematoma is associated with better chances of surviving free of severe disability after acute ICH. With the evolution of instrument and techniques, further trial should address the role of haematoma evacuation in deep ICH patients, the time window and difference between mini-invasive techniques.
Funding: Joint Global Health Trials (JGHT) funding scheme from the Department of Health and Social Care, the Foreign, Commonwealth & Development Office, the Medical Research Council and Wellcome Trust; the West China Hospital Outstanding Discipline Development 1-3-5 programme; National Health and Medical Research Council of Australia; Sichuan Credit Pharmaceutical; and Takeda (China).
Intracerebral haemorrhage management practices and adherence to the INTERACT3 care bundle in Latin America: Results from an international survey
(2025) Rosales, Julieta; Carbonera, Leonardo; De Souza, Ana; Rocha, Eva; Cano, Vanessa; Orjuela, Karen; Guerrero, Rodrigo; Delfino, Carlos; Nuñez, Marilaura; Munoz Venturelli, Paula; Gonzalez, Alejandro
Objective: To assess intracerebral hemorrhage (ICH) management practices and adherence to the INTERACT3 care bundle across Latin American countries.
Methods: We conducted a multi-national survey among neurologists, neurosurgeons, intensive care specialists, and emergency physicians. From August to December 2024, the survey was distributed across 19 Latin American countries. It assessed hospital characteristics, availability of an ICH code, adherence to INTERACT3 measures, and resource availability. Stroke leaders from the surveyed countries were involved in developing and disseminating the survey.
Results: Out of 580 respondents (mean age 40.25 years; 61.6% male), most worked in teaching (86%) and public hospitals (53.6%). Only 27.9% reported an ICH code at their institution. Adherence to INTERACT3 measures ranged from 57.2% (anticoagulation reversal) to 84.7% (blood pressure control), with just 44.5% reporting adherence to all four measures. Time-to-target was not measured by 65%, and only 53.9% maintained interventions for one week. Neuroimaging, neurosurgery, and hematology services were higher in private compared to public and mixed hospitals (p<0.001). ICH code availability was associated with private hospitals and emergency care specialists, while full adherence was more likely among intensive care specialists.
Conclusions: ICH management in Latin America is evolving, with increasing adoption of evidence-based practices. However, variability in adherence underscores the need for regional initiatives to standardize ICH care and ensure equitable implementation of best practices.
Vancomycin levels for Bayesian dose-optimization in critical care: a prospective cohort study
(2025) Dreyse, Natalia; Salazar, Nicole; Munita, Jose M.; Rello, Jordi; López, René
Background: Vancomycin dosing in critically ill patients typically requires monitoring the area under the concentration-time curve/minimum inhibitory
concentration (AUC/MIC), often using at least two vancomycin levels (VLs). However, the optimal number of VLs needed for accurate AUC/MIC estimation in
this population remains uncertain. This study aimed to determine the minimum number of VLs required to accurately estimate the AUC/MIC in critically ill
patients treated with intermittent infusion of vancomycin.
Methods: A prospective cohort study was conducted in critically ill patients, where VLs were obtained at peak, beta, and trough phases. Five AUC estimates were derived using PrecisePK™, a Bayesian software: AUC-1 [peak, beta (2 h after the end infusion), trough], AUC-2 (beta, trough), AUC-3 (peak, trough), AUC-4 (trough), and AUC-5 (only Bayesian prior, without VL). These estimates were compared for accuracy and bias (mean ± SEM) against the reference AUC calculated via the trapezoidal model (AUCRef).
Results: We enrolled 36 adult patients with age of 65 (52–77) years, moderate severity [APACHE II 10 (5–14) and SOFA 5 (4–6)], 6 of them in ECMO and 4 in renal replacement therapy. A total of 108 blood samples for VL were analyzed. The AUC-3 (0.976 ± 0.012) showed greater accuracy compared to AUC-4 (1.072 ± 0.032, p = 0.042) and AUC-5 (1.150 ± 0.071, p = 0.042). AUC-3 also demonstrated lower bias (0.053 ± 0.009) than AUC-4 (0.134 ± 0.026, p = 0.036) and AUC-5 (0.270 ± 0.060, p = 0.003). Bland–Altman analysis indicated better agreement between AUC-3 and AUC-2 with AUCRef.
Conclusion: Bayesian software using two vancomycin levels provides a more accurate and less biased AUC/MIC estimation in critically ill patients.
Assessing the impact of a single qualitative fecal immunochemical test on colonoscopy prioritization and mortality in risk-stratified patients with suspected colorectal cancer: a retrospective cohort study
(2025) Quezada, Felipe; Acevedo, Johanna; González, Maite; Tello, Andrea; Castillo, Richard; Morales, Carlos; Manríquez. Erik; Duran, Valentina; Mena, Felipe; Le-Bert, Catherine; Cabreras, Manuel; Fulle, Ángelo; Carvajal, Gonzalo; Briones, Pamela; Nervi, Bruno; Kusanovich, Rodrigo
Background: Performing fecal immunochemical tests in symptomatic individuals at low-or moderate risk for suspected colorectal cancer could help prioritize candidates for colonoscopies. The objective of this study was to assess the diagnostic accuracy of the fecal immunochemical test (FIT) in symptomatic individuals at low-or moderate risk of colorectal cancer and explore association with survival.
Methods: We conducted a retrospective cohort study between December 2016 and July 2024 from a single-center, public hospital in Chile. Adults (≥18 years-old) individuals were included, those with symptoms suggestive of colorectal cancer and set for evaluation via colonoscopy. Symptomatic individuals with suspected colorectal cancer were stratified as high risk or low/moderate risk by a trained nurse according to 2015 NICE guidelines. Subsequently, high risk patients were directly referred for colonoscopies, while low/moderate risk patients underwent a single qualitative FIT and prioritized to colonoscopy based on results. Main outcomes were FIT diagnostic accuracy for colorectal cancer, overall mortality, and colorectal cancer-specific mortality.
Findings: A total of 394 out of 1304 participants (30%) were classified as high risk. The remaining 910 (70%) were categorized as low/moderate risk and were referred for FIT. From these, 808 (89%) individuals were tested and had results for FIT. Regarding the diagnostic accuracy of the FIT, sensitivity was 96% and specificity reached 66.8%, with a negative value of 99.8%. Low/moderate risk positive FIT (FIT+) and high-risk participants had higher mortality rates vs. low/moderate risk negative FIT (FIT-) individuals. Time-to-event analysis confirmed a lower cumulative mortality in low/moderate risk FIT- patients. A multivariable Cox regression model showed a consistently lower risk of death in this group, while a non-significant trend towards increased mortality was observed in low/moderate risk FIT+ individuals after 30 months.
Interpretation: In symptomatic individuals at low or moderate risk, a single qualitative FIT was associated with high sensitivity and moderate specificity for colorectal cancer detection. FIT may help prioritize colonoscopy in low-resource settings, but further prospective validation is warranted.
Funding: This research was partially funded by ANIDFONDAP152220002 (CECAN).
Causas del abandono de embarazadas a la atención odontológica en atención primaria en chile. Un estudio cualitativo
(2026) Soto, Monserrat; Cantarutti, Cynthia; Pardo, Antonia; Ortúzar, Isabel; Jordán, Valentina; Moneva, Mariana; Madariaga, Pablo; Véliz, Claudia
Introducción: En Chile la atención odontológica para embarazadas está garantizada mediante Garantías Explícitas en Salud. Sin embargo, muchas mujeres que inician el tratamiento no lo completan. Las razones de este abandono han sido escasamente estudiadas desde la experiencia de las usuarias. Objetivo: Comprender el significado atribuido al tratamiento odontológico durante el embarazo y las razones que llevan a su abandono, desde la experiencia de mujeres que accedieron a las garantías. Metodología: Estudio cualitativo con análisis de contenido inductivo de entrevistas semiestructuradas a mujeres que no finalizaron el tratamiento odontológico en Atención Primaria de Salud. El muestreo fue por conveniencia. El análisis fue manual, independiente e incluyó validación de hallazgos con participantes. Resultado: Se realizaron once entrevistas, desde las cuales emergieron siete temas. El abandono se asoció a la dificultad para compatibilizar las horas con las exigencias cotidianas, agravada por la escasa flexibilidad horaria, los cambios de hora y la exclusión tras inasistencias. Se sumó un débil vínculo con el centro, con ausencia de rescate, rotación de profesionales y escasa información. Discusión: El abandono no se explicó por barreras clásicas
como el costo, el miedo o la baja valoración de la salud bucal, sino por la dificultad para compatibilizar las exigencias cotidianas con un programa poco flexible y por un vínculo institucional débil. Conclusión: Los programas para gestantes deberían asignar horas compatibles con la vida cotidiana, fortaleciendo el vínculo y seguimiento con el centro.
Introduction: In Chile dental care for pregnant women is guaranteed through the Explicit Health Guarantees system. However, many women who initiate treatment do not complete it. The reasons underlying treatment abandonment have been scarcely studied from the perspective of users. Objective: To understand the meaning attributed to dental treatment during pregnancy and the reasons leading to its abandonment, based on the experiences of women who accessed the guarantees. Methodology: A qualitative study was conducted using inductive content analysis of semi- structured interviews with women who did not complete dental treatment in Primary Healthcare. Convenience sampling was used; the analysis was performed manually and independently, and included validation of findings with participants. Result: Eleven interviews were conducted, from which seven themes emerged. Treatment abandonment was associated with difficulties in reconciling appointments with daily life demands, exacerbated by limited scheduling flexibility, appointment changes, and exclusion from the program after missed visits. A weak connection with the healthcare center was also identified, characterized by the absence of follow-up strategies, professional turnover, and limited information. Discussion: Treatment abandonment was not explained by traditional barriers such as cost, fear, or low oral health valuation, but rather by the difficulty of reconciling daily demands with an inflexible program and by a weak institutional relationship. Conclusion: Programs targeting pregnant women should provide appointment schedules compatible with daily life and strengthen patient–center follow-up and relationships to promote treatment continuity.
Gut Microbiota-Derived Extracellular Vesicles Influence Alcohol Intake Preferences in Rats
(2025) Díaz-Ubilla, Macarena; Figueroa-Valdés, Aliosha I.; Tobar, Hugo E.; Quintanilla, María Elena; Díaz, Eugenio; Morales, Paola; Berríos-Cárcamo, Pablo; Santapau, Daniela; Gallardo, Javiera; Gregorio, Cristian de; Ugalde, Juan; Rojas, Carolina; Gonzalez-Madrid, Antonia; Ezquer, Marcelo; Israel, Yedy; Alcayaga-Miranda, Francisca; Ezquer, Fernando
Growing preclinical and clinical evidence suggests a link between gutmicrobiota dysbiosis and problematic alcohol consumption.
Extracellular vesicles (EVs) are key mediators involved in bacteria-to-host communication. However, their potential role in mediating addictive behaviour remains unexplored. This study investigates the role of gut microbiota-derived bacterial extracellular vesicles (bEVs) in driving high alcohol consumption. bEVs were isolated from the gut microbiota of a high alcoholdrinking rat strain (UChB rats), either ethanol-naïve or following chronic alcohol consumption and administered intraperitoneally or orally to alcohol-rejecting male and femaleWistar rats. Both types of UChB-derived bEVs increased Wistar’s voluntary alcohol consumption (three bottle choice test) up to 10-fold (p < 0.0001), indicating that bEVs are able and sufficient to transmit drinking behaviour across different rat strains. Molecular analysis revealed that bEVs administration did not induce systemic or brain inflammation in the recipient animals, suggesting that the increased alcohol intake triggered by UChB-derived bEVs operates through an inflammation-independent mechanism. Furthermore,we demonstrate that the vagus nerve mediates the bEV-induced increase in alcohol consumption, as bilateral vagotomy completely abolished the high drinking behaviour induced by both intraperitoneally injected and orally administered bEVs. Thus, this study identifies bEVs as a novel mechanism underlying gut microbiota-induced high alcohol intake in a vagus nerve-dependent manner.
Candidate Interventions for Integrating Hypertension and Cardiovascular-Kidney-Metabolic Care in Primary Health Settings: HEARTS 2.0 Phase 1
(2025) Rosende, Andres; Romero, Cesar; DiPette, Donald; Brettler, Jeffrey; Van der Stuyft, Patrick; Satheesh, Gautam; Perel, Pablo; Chapman, Niamh; Moran, Andrew; Schutte, Aletta; Sharman, James; Irazola, Vilma; Huffman, Mark; Campbell, Norm; Salam, Abdul; Lanas, Fernando; Coca, Antonio; Garcia, Sebastian; Ferreiro, Alejandro; Lopez, Patricio; Rico, Jorge; Ridley, Emily; Picone, Dean; Flood, David; Piñeiro, Daniel; Neira, Carolina; Rodriguez, Gonzalo; Wellmann, Irmgardt; Orias, Marcelo; Rivera, Marcela; Villatoro, Matías; Onuma, Oyere; Ramroop, Shaun; Khan, Taskeen; Valdes, Yamile; Kunz, Weimar; Plavnik, Frida; Zuniga, Eric; Grassani, Ana; Tajer, Carlos; Zaidel, Ezequiel; Marin, Marcos; Cyr-Philbert, Shana; Amorin, Ignacio; Diaz, Miguel; Bortolotto, Luiz; Avezum, Alvaro; Ribeiro, Antonio; Tobe, Sheldon; Aumala, Teresa; Angell, Sonia; Lavados, Pablo; Ouriques, Sheila; Munera, Ana; Jaffe, Marc; Prabhakaran, Dorairaj; Parati, Gianfranco; Zhang, Xin Hua; Rodgers, Anthony; Yusuf, Salim; Whelton, Paul; Ordunez, Pedro
Background: HEARTS in the Americas is the regional adaptation of the WHO Global HEARTS Initiative, aimed at helping countries enhance hypertension and cardiovascular disease (CVD) risk management in primary care settings. Its core implementation tool, the HEARTS Clinical Pathway, has been adopted by 28 countries. To improve the care of hypertension, diabetes, and chronic kidney disease (CKD), HEARTS 2.0 was developed as a three-phase process to integrate evidence-based interventions into a unified care pathway, ensuring consistency across fragmented guidelines. This paper focuses on Phase 1, highlighting targeted interventions to improve and update the HEARTS Clinical Pathway.
Methods: First, the coordinating group defined the project's scope, objectives, principles, methodological framework, and tools. Second, international experts from different disciplines proposed interventions to enhance the HEARTS Clinical Pathway. Third, the coordinating group harmonized these proposals into unique interventions. Fourth, experts appraised the appropriateness of the proposed interventions on a 1-to-9 scale using the adapted RAND/UCLA Appropriateness Method. Finally, interventions with a median score above 6 were deemed appropriate and selected as candidates to enhance the HEARTS Clinical Pathway.
Results: Building on the existing HEARTS Clinical Pathway, 45 unique interventions were selected, including community-based screening, early detection and management of risk factors, lower blood pressure thresholds for diagnosing hypertension in high-CVD-risk patients, reinforcement of single-pill combination therapy, inclusion of sodium-glucose cotransporter-2 inhibitors for patients with diabetes, CKD, or heart failure, expanded roles for non-physician health workers in team-based care, and strengthened clinical documentation, monitoring, and evaluation.
Conclusion: HEARTS 2.0 Phase 1 identifies key interventions to integrate and improve hypertension and cardiovascular-kidney-metabolic care within primary care, enabling their seamless incorporation into a unified and effective clinical pathway. This process will inform an update to the HEARTS Clinical Pathway, optimizing resources, reducing care fragmentation, improving care delivery, and advancing health equity, thereby supporting global efforts to combat the leading causes of death and disability.