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GEMIN5 is a multifunctional protein involved in various aspects of RNA biology, including biogenesis of snRNPs and translation control. Reduced levels of GEMIN5 confer a differential translation to selective groups of mRNAs, and biallelic variants reducing protein stability or inducing structural conformational changes are associated with neurological disorders. Here, we show that upregulation of GEMIN5 can be detrimental as it modifies the steady state of mRNAs and enhances alternative splicing (AS) events of genes involved in a broad range of cellular processes. RNA-Seq identification of the mRNAs associated with polysomes in cells with high levels of GEMIN5 revealed that a significant fraction of the differential AS events undergo translation. The association of mRNAs with polysomes was dependent on the type of AS event, being more frequent in the case of exon skipping. However, there were no major differences in the percentage of genes showing open-reading frame disruption. Importantly, differential AS events in mRNAs engaged in polysomes, eventually rendering non-functional proteins, encode factors controlling cell growth. The broad range of mRNAs comprising AS events engaged in polysomes upon GEMIN5 upregulation supports the notion that this multifunctional protein has evolved as a gene expression balancer, consistent with its dual role as a member of the SMN complex and as a modulator of protein synthesis, ultimately impinging on cell homoeostasis.

Los virus herpes simple (Herpes Simplex Virus, HSV) de tipo 1 y 2 producen la infección de transmisión sexual más común en mujeres, con mayor incidencia en los países en desarrollo. Además de generar secuelas principalmente neurológicas en el recién nacido, cuando la primoinfección ocurre durante el periodo perinatal, puede diseminarse y producir gran morbimortalidad de la madre y el neonato. A pesar de contarse con pruebas de laboratorio confiables, el diagnóstico de la infección por HSV durante el periodo perinatal es complejo, pues sus manifestaciones clínicas varían desde la forma diseminada hasta la asintomática o se pueden producir síntomas inespecíficos sin lesiones en piel o mucosas, por lo que es fundamental tener la sospecha clínica. Se presenta el caso de una madre con infección diseminada por HSV de tipo 2 que presentó hepatitis viral y cuyo neonato falleció, resaltándose la importancia de sospechar la infección por HSV en una mujer gestante febril con compromiso sistémico durante el periodo perinatal, aun en ausencia de brote.

Abstract Grape pomace is the main byproduct of the wine industry and an important source of dietary fiber and phenolic compounds. Grape pomace powder (GPP) partially substituted 8, 10, 12, 15, and 25% of the wheat flour in bread formulations. The proximate composition, total dietary fiber content, phenolic compounds, texture profile, color, and bioaccessibility of phenolic compounds in vitro were measured in the bread. Bread sensory acceptance by consumers was determined using a 9-point hedonic scale. Compared with the control bread (CB), the 8% GPB-substituted bread presented the best results and exhibited an increase in total protein content (7.5%) and total dietary fiber content (6.1%). The total phenolic content was greater in GPB (5.1 mg GAE/g) than in CB (2.1 mg GAE/g). Adding GPP to the bread affected the color, and the color of the GPB-treated bread was darker than that of the CB-treated bread. Still, no significant differences were detected regarding the texture profile or consumer sensory acceptance between the GPB-treated and CB-treated bread. The in vitro analysis of phenolic compound bioaccessibility revealed no differences between the two samples during gastrointestinal digestion. GPP is an interesting byproduct that can be used in bakery. The replacement of 8% of the bread with GPP increased the nutritional content of the bread, particularly the protein, total dietary fiber, and total phenolic content, without affecting the texture or sensory acceptance of the bread. To understand the possible beneficial effect of GPB on consumers, further research on the bioavailability of phenolic compounds and the impact of dietary fiber increment needs to be assessed. Graphical Abstract

Insulin-like growth factor-1 (IGF-1) elicits a variety of effects on the regulation of oxidative stress, a topic that remains shrouded in controversy. This intricate regulation plays a pivotal role in the aging process and its associated diseases. Notably, it centers around the challenge posed by endogenous antioxidant defenses, which often struggle to counteract free radicals-induced damage to various neural cell macromolecules. The interplay between IGF-1 and oxidative stress holds significant implications. Both factors are intertwined in the context of degenerative and inflammatory disruptions within the central nervous system (CNS), giving rise to dysfunctions in neurons and glial cells. These dysfunctions encompass detrimental outcomes such as excitotoxicity, neuronal attrition, and axonal impairment, all of which are closely related to behavioral irregularities. However, the complexities of IGF-1’s impact remain a topic of debate. Divergent research findings present IGF-1 as both an antioxidative agent and a catalyst to produce reactive oxygen species (ROS) in various neuropathologies. This diversity of outcomes has contributed to the ongoing controversy in the field. The present theoretical review undertakes a comprehensive vision, shedding light on the role of IGF-1 as a regulator within the mechanistic framework of oxidative stress responses. This regulatory role serves as the basis for the emergence of progressive neurodegenerative and neuroinflammatory conditions. Particularly compelling is the exploration of IGF-1 as a potential target for promising therapeutic interventions in this domain. However, the review also highlights significant limitations, including the considerations to work with this factor and the need for further research to clarify IGF-1’s role. Future perspectives should focus on refining our understanding of IGF-1’s mechanisms and exploring its therapeutic potential in more detail.

Abstract Background The healing process after tooth removal involves bone remodelling which implies some loss of alveolar bone volume. Among materials proposed for minimising this remodelling and preserving the bone, autologous dental tissue is a promising option, but more data are needed. In this context, we evaluated size and density changes using cone beam computed tomography in autologous dental material (ADM)-preserved sockets compared to controls, and assessed biological responses by histological analysis. Methods A split-mouth study was conducted including 22 patients, who underwent removal of ≥ 2 single-rooted teeth with intact sockets, assigning one socket to the experimental group which received ADM for alveolar preservation and another to the control group, which only underwent blood clot stabilisation. Cone beam computed tomography was performed postoperatively (week 0) and at weeks 8 and 16 to assess socket size and bone density. Histological analysis was carried out on trephine biopsies taken (Ø4 × 4.5 mm) from the experimental group. Results Less horizontal shrinkage was observed in the ADM group, especially at week 16 considering the group-by-time interaction for the following variables: difference in height between the lingual and buccal alveolar crests (-1.00; p

Abstract Background Breast cancer is the most common cancer in women. Cancer cells can persist in a prolonged dormant state for years without any clinical evidence of disease creating an urgent need to better understand the molecular mechanisms leading to relapse. This study aimed to identify extracellular matrix (ECM) components associated with hypoxia-induced breast cancer dormancy. The effects of selected ECM proteins on breast cancer cell proliferation were analyzed, along with their correlation with established prognostic markers in human breast cancer tissue. Materials and methods Screening of extracellular matrix proteins was performed in hypoxia-induced dormant MCF-7 breast cancer cells. Proliferation of MCF-7 cells in vitro was subsequently determined in the presence of recombinant ColVII. Adipose tissue-derived mesenchymal stem cells (AdMSCs) subpopulation overexpressing ColVII were indirectly isolated by ColVII receptor integrin-α6 specific antibodies. AdMSCs- MCF-7 3D spheroid cultures were generated to model solid tumour conditions. In addition, the association between ColVII and various prognostic markers was evaluated in clinical samples of human breast cancer tissue. Results Dormant MCF-7 cells showed an elevated expression of ColVII while MCF-7 cells cultured on ColVII exhibited reduced proliferation in vitro. In AdMSCs-MCF-7 3D spheroids, a reduced proliferation of MCF-7 cells was observed in Int-α6+/ ColVIIhigh compared with Int-α6-/ ColVIIlow AdMSCs spheroids. In human tissue, high ColVII expression correlated to several positive prognostic markers. Staining for Cytokeratin-5 revealed that ColVIIhigh-expressing cells were predominantly myoepithelial cells. Conclusion ColVII is associated with reduced proliferation of breast cancer cells in vitro. ColVII is strongly expressed in myoepithelial cells and in breast cancer tissue the high ColVII expression correlates with several well-known positive prognostic markers, highlighting its potential as a prognostic marker in breast cancer.

Abstract Background Sepsis is a frequent cause of admission to intensive care units (ICUs). High mortality rates are estimated globally, and in our country, few studies have reported one-year survival. The objective of this study is to determine one-year survival in patients with sepsis admitted to the ICU in Colombia, compared with the survival of patients admitted for other conditions. Methods Retrospective cohort study using administrative databases from the Ministry of Health of Colombia. One-year survival and the adjusted hazard ratio for survival, adjusted for comorbidities included in the Charlson Index, were determined using a Cox proportional hazards model for patients admitted for other causes as well as for those admitted for sepsis. This was then compared with an inverse propensity score weighting model. Results A total of 116.407 patients were initially admitted to the ICUs, with 12.056 (10.36%) diagnosed with sepsis. Within the first year, 4.428 (36.73%) patients died due to sepsis. Age and male gender were associated with an increased risk of death from sepsis, and the covariates associated with one-year mortality were as follows: age over 80 years with HR 9.91 (95% CI: 9.22–10.65), renal disease with HR 3.16 (95% CI: 3.03–3.29), primary tumoral disease with HR 2.07 (95% CI: 1.92–2.23), liver disease with HR 2.27 (95% CI: 2.07–2.50), and metastatic solid tumor with HR 2.03 (95% CI: 1.92–2.15). Conclusion This study revealed a high one-year sepsis mortality rate in the population, associated with variables such as age over 80 years, the presence of renal disease, liver disease, connective tissue diseases, and cancer. Men exhibited higher mortality compared to women.

Abstract Adeno-associated viruses (AAVs) are promising gene therapy vectors, but challenges arise when treating patients with preexisting neutralizing antibodies. Worldwide seroprevalence studies provide snapshots of existing immunity in diverse populations. Owing to the uniqueness of the Basque socio-geographical landscape, we investigated the seroprevalence of eight AAV serotypes in residents of the Basque Country. We found the highest seroprevalence of AAV3, and the lowest seroprevalence of AAV9. Additionally, less than 50% of the Basque population has neutralizing antibodies against AAV4, AAV6, and AAV9. Our findings provide insight into AAV infections in the Basque region, public health, and the development of AAV-based therapeutics.

AbstractThis study aims to investigate the correlation between components of financial inclusion and the growth of manufacturing microenterprises in Bogotá, focusing on the period from 2012 to 2016. Utilizing data sourced from the ‘Annual Survey of Micro Establishments’ provided by National Administrative Department of Statistics, the research includes an extensive literature review, a meticulous comparison of the financial inclusion components employed by these microenterprises and an evaluation of their impact on business growth using a linear panel data model with random effects. Findings suggests that microenterprises utilizing financial products exhibit sustained growth over time compared to those that do not. Furthermore, this study introduces an innovative perspective by quantitatively addressing the relationship between financial inclusion and the business growth of such companies in developing countries. As a recommendation, microenterprises should focus their efforts on establishing robust financial management practices, formalizing through RUT (Single Taxpayer Registry), adopting digitalization strategies and advocating for equitable financial inclusion policies. While the study contributes to the literature on financial inclusion, a more in-depth qualitative exploration of cultural and idiosyncratic factors is advised.

El uso de biofertilizantes ha aumentado en las últimas décadas como una alternativa sostenible al uso de agroinsumos químicos. Aunque aún el uso de agroquímicos es más común que el de biofertilizantes, sí se ha notado cada vez una tendencia hacia métodos más sostenibles, que incluyen a estos últimos. Si bien Colombia es un país con un gran potencial biotecnológico y una alta biodiversidad, no es un líder en la producción de biofertilizantes, lo cual limita su capacidad de solucionar los requerimientos alimentarios de una manera sostenible. Por tal motivo, esta revisión busca entender las tendencias actuales en materia de biofertilizantes colombianos, desde la ciencia que respalda la producción de estos, hasta los desafíos que enfrenta el país en el uso de la biodiversidad microbiana para la agricultura. Este proceso se realizó por medio de una búsqueda de información en bases de datos indexadas, recopilando información de biofertilizantes que se encuentran registrados en Colombia, y teniendo en cuenta características como la composición microbiana, metodologías, tendencias del mercado, composición del bioproducto, formulación y normativas vigentes. Finalmente, se presenta una prospección futura en cuanto al destino de los biofertilizantes en Colombia, su posible implementación, efectos en la producción agrícola y métodos de aceleración de su desarrollo, con miras a la optimización de su uso y adopción en el país.

Parkinson’s disease is a pathology with a wide range of in vivo and in vitro models available. Among these, the SH-SY5Y neuroblastoma cell line is one of the most employed. This model expresses catecholaminergic markers and can differentiate and acquire various neuronal phenotypes. However, challenges persist, primarily concerning the variability of growth media, expression of dopaminergic markers, and a wide variety of differentiation protocols have been reported in the literature without direct comparison between them. This lack of standardized differentiation conditions impacts result reproducibility and it makes it very difficult to compare the results obtained from different research groups. An alternative cellular model is the neuroblastoma BE (2)-M17 which exhibits a high basal expression of numerous dopaminergic markers such as tyrosine hydroxylase (TH), vesicular monoamine transporter 2 (VMAT2), and dopamine transporter (DAT). The BE (2)-M17 cells show neuronal properties, grows rapidly in conventional media, and can easily be differentiated to increase their dopaminergic phenotype. In this review, we will thoroughly explore the properties of the BE (2)-M17 cell line and discuss its potential as an excellent model for studying Parkinson’s disease.

Cardiopulmonary exercise testing allows for a comprehensive assessment of the mechanism of exercise limitation in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Competitive pathophysiologic mechanisms may affect the clinical interpretation of cardiopulmonary disease as they relate to dyspnea, leg fatigue, and exercise intolerance.

Over the past decades, health care systems have significantly evolved due to aging populations, chronic diseases, and higher-quality care expectations. Concurrently with the added health care needs, information and communications technology advancements have transformed health care delivery. Technologies such as telemedicine, electronic health records, and mobile health apps promise enhanced accessibility, efficiency, and patient outcomes, leading to more personalized, data-driven care. However, organizational, political, and cultural barriers and the fragmented approach to health information management are challenging the integration of these technologies to effectively support health care delivery. This fragmentation collides with the need for integrated care pathways that focus on holistic health and wellness. Catalonia (northeast Spain), a region of 8 million people with universal health care coverage and a single public health insurer but highly heterogeneous health care service providers, has experienced outstanding digitalization and integration of health information over the past 25 years, when the first transition from paper to digital support occurred. This Viewpoint describes the implementation of health ITs at a system level, discusses the hits and misses encountered in this journey, and frames this regional implementation within the global context. We present the architectures and use trends of the health information platforms over time. This provides insightful information that can be used by other systems worldwide in the never-ending transformation of health care structure and services.

IntroductionComprehensive, hybrid cardiac rehabilitation (CR) models have been scantly investigated in heart failure (HF) populations, particularly in low-resource settings. CO-CREATION-HF aims to evaluate the effectiveness of such a model compared to supervised exercise alone.Methods and analysisA 2 parallel-arm, multi-center randomized clinical superiority trial will be conducted with blinded outcome assessment. 152 HF patients (NYHA class II or III) will be recruited consecutively, and randomly assigned using permuted blocks; allocation will be concealed. The 12-week intervention will include evaluation, medical and nurse management, aerobic interval training, resistance exercise training, psychosocial support, and education. These will initially be delivered in a center, transitioning to home in 4 stages. Controls will receive similar management, but face-to-face continuous aerobic exercise sessions and resistance exercises. The main outcomes are cardiorespiratory fitness (VO2 max), functional capacity (m from 6 MWT), and quality of life (Minnesota Living with Heart Failure Questionnaire). Program adherence and completion, NT-proBNP, functioning, all-cause and HF-specific mortality and hospitalization, muscle strength, adverse events and cost will be secondary outcomes. These will be measured at baseline, end of intervention, and 12-month follow-up. The sample size was calculated considering 90% power, a significance level of 5%, a between-group difference equivalent to 1/2 MET, and a 10% potential loss to follow-up. Intention-to-treat analysis will be considered. Between-group differences will be assessed using Student's t-tests or Z-tests along with 95% confidence intervals, and the rate ratio will be computed to compare mortality.Ethics and disseminationThe study protocol and the Informed Consent form were approved by Ethical Committees at the Universidad de La Frontera (No. 081-23) and each center participating. Research findings will be disseminated to the scientific community and will be shared with relevant stakeholder groups and policy-makers. Finally, investigators shall reach HF patients via various dissemination channels such as social media. Clinical Trial Registrationclinicaltrials.gov, identifier (NCT06313684).

Abstract An outstanding question in the geological evolution of the Chilean Andes is the cause of the westward shift and relocation of magmatism from the High Andes (HA) to the Coastal Cordillera (CC) during the Late Triassic, Pre–Andean stage. The spatiotemporal distribution of Permian–Triassic–Jurassic igneous rocks in northern‐central Chile (20°S–32°S) reveals a significant westward magmatic shift of ∼120 km during the Norian time. Despite diverse proposed models, the precise geodynamic mechanism behind this shift remains unclear. To address this, we used 2D numerical modeling to investigate two contrasting scenarios: (a) subduction rollback and (b) subduction transference/jump and reinitiation by terrane accretion. Our modeling results strongly support Scenario B, where mantle density and the size of the oceanic plateau are crucial for triggering subduction jump and reinitiation. This model aligns with geological and geophysical evidence and offers new insights into unraveling the Pre– and Early–Andean evolution.

Multidose drug dispensing (MDD) is the dispensing of different drugs in dose bags containing one, some, or all units of medicine that a patient needs to take at specific times. The aim of this narrative review is to provide an overview of the literature describing the use of MDD systems in community healthcare settings in patients with multimorbidity and polypharmacy. A literature search identified 14 studies examining adherence, medication knowledge, quality of drug prescription (including inappropriate drug use, drug-drug interactions), medication incidents, and drug changes after MDD initiation, as well as healthcare professional (HCP) and patient perspectives. There are limited data on MDD in community healthcare settings, particularly on outcomes such as adherence. Studies are mostly from Northern Europe. Patients selected for MDD are more likely to be older, female, cognitively impaired, and have a higher number of disease diagnoses and drugs than those who do not receive drugs through MDD. MDD is generally initiated for patients who have decreased capacity for medication management. Several advantages of MDD have been reported by patients and HCPs, and studies indicate that MDD can be improved by medication review, defining clear roles and responsibilities of HCPs in the medication management chain, and comprehensive follow-up of patients. Future development, implementation, and assessment of MDD systems in community healthcare should be designed in collaboration with HCPs and patients, to identify ways to optimize the systems and improve patient outcomes.

Abstract Background Structural income inequality – the uneven income distribution across regions or countries – could affect brain structure and function, beyond individual differences. However, the impact of structural income inequality on the brain dynamics and the roles of demographics and cognition in these associations remains unexplored. Methods Here, we assessed the impact of structural income inequality, as measured by the Gini coefficient on multiple EEG metrics, while considering the subject‐level effects of demographic (age, sex, education) and cognitive factors. Resting‐state EEG signals were collected from a diverse sample (countries = 10; healthy individuals = 1394 from Argentina, Brazil, Colombia, Chile, Cuba, Greece, Ireland, Italy, Turkey and United Kingdom). Complexity (fractal dimension, permutation entropy, Wiener entropy, spectral structure variability), power spectral and aperiodic components (1/f slope, knee, offset), as well as graph‐theoretic measures were analysed. Findings Despite variability in samples, data collection methods, and EEG acquisition parameters, structural inequality systematically predicted electrophysiological brain dynamics, proving to be a more crucial determinant of brain dynamics than individual‐level factors. Complexity and aperiodic activity metrics captured better the effects of structural inequality on brain function. Following inequality, age and cognition emerged as the most influential predictors. The overall results provided convergent multimodal metrics of biologic embedding of structural income inequality characterised by less complex signals, increased random asynchronous neural activity, and reduced alpha and beta power, particularly over temporoposterior regions. Conclusion These findings might challenge conventional neuroscience approaches that tend to overemphasise the influence of individual‐level factors, while neglecting structural factors. Results pave the way for neuroscience‐informed public policies aimed at tackling structural inequalities in diverse populations.

Summary: Background: Surgical care holds significant importance in healthcare, especially in low and middle-income countries, as at least 50% of the 4.2 million deaths within the initial 30 days following surgery take place in these countries. The Lancet Commission on Global Surgery proposed six indicators to enhance surgical care. In Colombia, studies have been made using secondary data. However, strategies to reduce perioperative mortality have not been implemented. This study aims to describe the fourth indicator, perioperative mortality rate (POMR), with primary data in Colombia. Methods: A multicentre prospective cohort study was conducted across 54 centres (hospitals) in Colombia. Each centre selected a 7-day recruitment period between 05/2022 and 01/2023. Inclusion criteria involved patients over 18 years of age undergoing surgical procedures in operating rooms. Data quality was ensured through a verification guideline and statistical analysis using mixed-effects multilevel modelling with a case mix analysis of mortality by procedure-related, patient-related, and hospital-related conditions. Findings: 3807 patients were included with a median age of 48 (IQR 32–64), 80.3% were classified as ASA I or II, and 27% of the procedures had a low-surgical complexity. Leading procedures were Orthopedics (19.2%) and Gynaecology/Obstetrics (17.7%). According to the Clavien–Dindo scale, postoperative complications were distributed in major complications (11.7%, 10.68–12.76) and any complication (31.6%, 30.09–33.07). POMR stood at 1.9% (1.48–2.37), with elective and emergency surgery mortalities at 0.7% (0.40–1.23) and 3% (2.3–3.89) respectively. Interpretation: The POMR was higher than the ratio reported in previous national studies, even when patients had a low–risk profile and low-complexity procedures. The present research represents significant public health progress with valuable insights for national decision-makers to improve the quality of surgical care. Funding: This work was supported by Universidad del Rosario and Fundación Cardioinfantil-Instituto de Cardiología grant number CTO-057-2021, project-ID IV-FGV017.