ABSTRACT
Background: Stigma toward child and adolescent mental health problems among parents has been understudied, despite its importance. Method: Sociodemographic variables, stigma associated with mental health problems in childhood and adolescence, myths about suicide, familiarity with mental health, and seeking professional help were assessed in a cross-sectional study in a Spanish sample (N = 268). Descriptive analyses, mean difference and regression models were carried out. Results: The results reveal medium levels of stigma, the presence of myths about suicide and average familiarity with mental health. Mothers and a higher level of education, showed lower levels of stigma and fewer myths about suicide. A regression model explains the 44% of the variance with myths about suicide, stigma and familiarity with mental health as predictors of seeking professional help attitudes. Conclusions: Stigma, myths surrounding suicide, and parental unfamiliarity with mental health may act as barriers to appropriate diagnosis and treatment. Practical implications and recommendations are discussed.(AU)
Antecedentes: La estigmatización de los problemas de salud mental en niños y adolescentes en los padres y madres no se ha estudiado lo suficiente a pesar de su importancia. Método: Se evaluaron variables sociodemográficas, el estigma asociado con los problemas de salud mental en la infancia y la adolescencia, mitos sobre el suicidio, conocimiento de la salud mental y la búsqueda de ayuda profesional en un estudio exploratorio transversal en una muestra española de padres y madres (N = 268). Se realizaron análisis descriptivos, de diferencia de medias y modelos de regresión. Resultados: Los resultados revelan un nivel medio de estigma, la presencia de mitos sobre el suicidio y un conocimiento medio con la salud mental. Las madres y un mayor nivel educativo mostraron menores niveles de estigma y menos mitos sobre el suicidio. El 44% de la varianza de la búsqueda de ayuda profesional se explica a través de los mitos sobre el suicidio, el estigma y el conocimiento de la salud mental como predictores de las actitudes de búsqueda de ayuda profesional. Conclusiones: Se establecen recomendaciones prácticas, subrayando cómo el estigma, los mitos sobre el suicidio y la falta de conocimiento de los progenitores de la salud mental pueden actuar como barreras para un diagnóstico y tratamiento adecuados. Se discuten las implicaciones prácticas y las recomendaciones.(AU)
Subject(s)
Humans , Male , Female , Child , Adolescent , Mental Health , Child Health , Adolescent Health , Stereotyping , Adolescent Behavior , Suicide , Cross-Sectional Studies , Psychology, Clinical , Psychology, Child , Psychology, AdolescentABSTRACT
While antisense oligonucleotides (ASOs) are used in the clinic, therapeutic development is hindered by the inability to assay ASO delivery and activity in vivo. Accordingly, we developed a dual-fluorescence, knockin mouse model that constitutively expresses mKate2 and an engineered EGFP that is alternatively spliced in the presence of ASO to induce expression. We first examined free ASO activity in the brain following intracerebroventricular injection revealing EGFP splice-switching is both ASO concentration and time dependent in major central nervous system cell types. We then assayed the impact of lipid nanoparticle delivery on ASO activity after intravenous administration. Robust EGFP fluorescence was observed in the liver and EGFP+ cells were successfully isolated using fluorescence-activated cell sorting. Together, these results show the utility of this animal model in quantifying both cell-type- and organ-specific ASO delivery, which can be used to advance ASO therapeutics for many disease indications.
Subject(s)
Oligonucleotides, Antisense , Oligonucleotides , Mice , Animals , Liver/metabolism , Administration, Intravenous , Coloring Agents/metabolismABSTRACT
Heterozygous mutations in the granulin (GRN) gene are a leading cause of frontotemporal lobar degeneration with TDP-43 aggregates (FTLD-TDP). Polymorphisms in TMEM106B have been associated with disease risk in GRN mutation carriers and protective TMEM106B variants associated with reduced levels of TMEM106B, suggesting that lowering TMEM106B might be therapeutic in the context of FTLD. Here, we tested the impact of full deletion and partial reduction of TMEM106B in mouse and iPSC-derived human cell models of GRN deficiency. TMEM106B deletion did not reverse transcriptomic or proteomic profiles in GRN-deficient microglia, with a few exceptions in immune signaling markers. Neither homozygous nor heterozygous Tmem106b deletion normalized disease-associated phenotypes in Grn -/-mice. Furthermore, Tmem106b reduction by antisense oligonucleotide (ASO) was poorly tolerated in Grn -/-mice. These data provide novel insight into TMEM106B and GRN function in microglia cells but do not support lowering TMEM106B levels as a viable therapeutic strategy for treating FTD-GRN.
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Background: The evaluation of a three-dimensional structure with a two-dimensional imaging technique makes intracoronary diagnostic techniques essential, especially in the setting of acute myocardial infarction (AMI) when no apparent coronary lesions are detected. Expert consensus recommend their use in certain scenarios such as angiographically ambiguous disease and identification of the culprit lesion. Although both intravascular ultrasound and optical coherence tomography (OCT) allow the characterization of the atherosclerotic plaque and assess the immediate and long-term results of stent implantation, they have their own benefits and limitations that make them ideal for different types of coronary lesions. Case summary: We present the case of a lateral ST-elevation myocardial infarction with no evident coronary lesions in angiography, in which OCT not only allowed us to confirm a diagonal branch occlusion, but it also became crucial to locate the occlusion point and to guide the procedure, allowing complete revascularization of the culprit lesion that otherwise could have been missed. Discussion: To know the actual limitations of conventional coronary angiography to adequately assess coronary disease, intracoronary diagnostic techniques are key to evaluate the underlying mechanisms of the event, especially in the setting of AMI when no clear culprit lesion has been identified. They can be of great value to locate and revascularize acute occlusions that could go unnoticed on the angiogram, guiding the revascularization and stent implantation and, therefore, preventing myocardial injury that could become irreversible when coronary disease is not treated promptly.
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Introduction: Oncolytic viruses (OVs) represent a novel therapeutic strategy in oncology due to their capability to selectively infect and replicate in cancer cells, triggering a direct and/or immune-induced tumor lysis. However, the mechanisms governing OV pharmacokinetics are still poorly understood. This work aims to develop a physiologically based pharmacokinetic model of the novel OV, V937, in non-tumor-bearing mice to get a quantitative understanding of its elimination and tissue uptake processes. Materials and methods: Model development was performed using data obtained from 60 mice. Viral levels were quantified from eight tissues after a single intravenous V937 dose. An external dataset was used for model validation. This test set included multiple-dose experiments with different routes of administration. V937 distribution in each organ was described using a physiological structure based on mouse-specific organ blood flows and volumes. Analyses were performed using the non-linear mixed-effects approach with NONMEM 7.4. Results: Viral levels showed a drop from 108 to 105 copies/µg RNA at day 1 in blood, reflected in a high estimate of total clearance (18.2 mL/h). A well-stirred model provided an adequate description for all organs except the muscle and heart, where a saturable uptake process improved data description. The highest numbers of viral copies were observed in the brain, lymph node, kidney, liver, lung, and spleen on the first day after injection. On the other hand, the maximum amount of viral copies in the heart, muscle, and pancreas occurred 3 days after administration. Conclusion: To the best of our knowledge, this is the first physiologically based pharmacokinetic model developed to characterize OV biodistribution, representing a relevant source of quantitative knowledge regarding the in vivo behavior of OVs. This model can be further expanded by adding a tumor compartment, where OVs could replicate.
ABSTRACT
Antisense oligonucleotide (ASO) therapeutics are being investigated for a broad range of neurological diseases. While ASOs have been effective in the clinic, improving productive ASO internalization into target cells remains a key area of focus in the field. Here, we investigated how the delivery of ASO-loaded lipid nanoparticles (LNPs) affects ASO activity, subcellular trafficking, and distribution in the brain. We show that ASO-LNPs increase ASO activity up to 100-fold in cultured primary brain cells as compared to non-encapsulated ASO. However, in contrast to the widespread ASO uptake and activity observed following free ASO delivery in vivo, LNP-delivered ASOs did not downregulate mRNA levels throughout the brain after intracerebroventricular injection. This lack of activity was likely due to ASO accumulation in cells lining the ventricles and blood vessels. Furthermore, we reveal a formulation-dependent activation of the immune system post dosing, suggesting that LNP encapsulation cannot mask cellular ASO backbone-mediated toxicities. Together, these data provide insights into how LNP encapsulation affects ASO distribution as well as activity in the brain, and a foundation that enables future optimization of brain-targeting ASO-LNPs.
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Background: The SARS-CoV-2 pandemic affected the school-aged population because of the disease itself and due to the measures applied for prevention and control of the infection. The aim of the study was to evaluate the effect of population-based vaccination against COVID-19 on the incidence of infection in school settings. Material and Methods: A retrospective descriptive study of COVID-19 cases and school outbreaks was carried out at the province level. Students, teachers and staff from different educational stages of the schools were included. The outcome measure was the incidence according to educational stage, case profile and clinic during the first of the academic year 2020/2021 versus the same period 2021/2022. Results: The total incidence of SARS-CoV-2 in classrooms was 2,470 cases per 100,000 population in the first trimester of the academic year 2020/2021 and 2,720 cases per 100,000 population in the same period 2021/2022. The number of reported school outbreaks was 7 times higher in this second period; and the risk of infection in classrooms over 12 years of age (students and teachers) was reduced by 43.1% (vaccinated in high percentage). Conclusions: This study shows a reduction in transmission of SARS-CoV-2 infection in students of higher educational stages (secondary and high school) during the first of the academic year 2021/2022 (group with high vaccination coverage at the beginning of the period) compared to the previous school year (without vaccination).
ABSTRACT
The Anisakis larvae presence in fish for human consumption is a health risk that needs to be monitored. The anchovy is a fish that is highly appreciated by consumers and that can harbour Anisakis. It is thus necessary to periodically evaluate the presence of anisakid larvae in them. So, anchovies from Iberian Peninsula coasts were analysed. Fish examination for macroscopic nematodes showed L3s of both Anisakis type I and Hysterothylacium aduncum. The Anisakis prevalence varies with the catching area and the fish size. The muscle prevalence was 7.45% (mean intensity 1.75; range 1-5). Molecular analysis showed 110 A. simplex s.s. (17 in muscle), 22 A. pegreffii (3) and 7 hybrid genotype individuals (1). Considering that most of the Iberian Peninsula coasts are a sympatry area between these two Anisakis species, it has been observed that A. simplex s.s./A. pegreffii ratio increases from south to north in a clockwise direction. Also, 19 larvae were detected on the fish surface from the Bay of Biscay, indicating the ability of these larvae to migrate after the fish death. The A. simplex s.s./A. pegreffii larvae proportion found on the anchovy surface is similar to the found in viscera and lower than in muscle, suggesting that most of the larvae migrating to the surface must have come from the visceral package. This confirms the importance of removing fish viscera immediately after capture, for those fish species where this is possible. As both species cause anisakiasis/anisakidosis, these data show a real risk to human health, especially in dishes highly prized in Mediterranean countries prepared with raw or semi-raw anchovies.
Subject(s)
Anisakiasis , Anisakis , Fish Diseases , Animals , Humans , Anisakiasis/parasitology , Anisakis/physiology , Europe , Fishes/parasitology , Food Parasitology , LarvaABSTRACT
Caveolae are nanoscopic and mechanosensitive invaginations of the plasma membrane, essential for adipocyte biology. Transmission electron microscopy (TEM) offers the highest resolution for caveolae visualization, but provides complicated images that are difficult to classify or segment using traditional automated algorithms such as threshold-based methods. As a result, the time-consuming tasks of localization and quantification of caveolae are currently performed manually. We used the Keras library in R to train a convolutional neural network with a total of 36,000 TEM image crops obtained from adipocytes previously annotated manually by an expert. The resulting model can differentiate caveolae from non-caveolae regions with a 97.44% accuracy. The predictions of this model are further processed to obtain caveolae central coordinate detection and cytoplasm boundary delimitation. The model correctly finds negligible caveolae predictions in images from caveolae depleted Cav1-/- adipocytes. In large reconstructions of adipocyte sections, model and human performances are comparable. We thus provide a new tool for accurate caveolae automated analysis that could speed up and assist in the characterization of the cellular mechanical response.
ABSTRACT
Based on knowledge of child development, this exploratory study focuses on the quality of touch during the care of babies in early childhood facilities. It also examines the place given to affect in the interaction between professionals and children.
Subject(s)
Child Day Care Centers , Touch , Child , Infant , Child, Preschool , Humans , Day Care, MedicalABSTRACT
The aim of this study was to explore the role of stigma in different diagnoses of mental illness. A cross-sectional study (N = 255) was developed in two groups: users of a rehabilitation network for people with severe mental illness (Group-I) and people with common diagnoses in an ambulatory psychiatric service (Group-II). Internalized stigma, social stigma, self-esteem, and sociodemographic variables were measured. Mean comparisons, ANOVAs, and independent linear regression models were carried out. Similar overall scores were obtained for the internalized stigma, but Group-I reported more discrimination and resistance to stigma and also had less social stigma. The regression model for Group-I revealed social stigma and self-esteem as predictors, while in Group-II only self-esteem was significant. The study reveals differences in internalized stigma according to the care resource and diagnoses, suggesting different intervention lines and underlining the importance of further research on this topic. (AU)
El objetivo de este estudio ha sido explorar el papel del estigma en los diferentes diagnósticos de la enfermedad mental. Se llevó a cabo un estudio transversal (N = 255) en dos grupos: usuarios de una red de rehabilitación para personas con enfermedad mental grave (grupo I) y personas con diagnósticos comunes en un servicio psiquiátrico ambulatorio (grupo II). Se midió el estigma internalizado, el social, la autoestima y las variables sociodemográficas. Se llevaron a cabo comparaciones medias, ANOVA y modelos de regresión lineal independientes. Se obtuvieron puntuaciones generales similares para el estigma internalizado, pero el grupo I manisfestó más discriminación y resistencia al estigma y también menor estigma social. El modelo de regresión para el grupo I mostró como predictores el estigma social y la autoestima, mientras que en el grupo II sólo la autoestima era significativa. El estudio muestra diferencias en el estigma internalizado según el recurso de atención y los diagnósticos, lo que sugiere diferentes líneas de intervención y subraya la importancia de seguir investigando en este tema. (AU)
Subject(s)
Humans , Young Adult , Adult , Middle Aged , Aged , Social Stigma , Mental Health , Self Concept , Mental Disorders , Cross-Sectional Studies , Mental Health ServicesABSTRACT
Introducción: Existen numerosos procedimientos para conseguir un lecho óseo adecuado para colocar implantes tras la pérdida de dientes naturales. En los últimos años se han propuesto técnicas para la preservación del lecho tras la extracción dental. Los injertos de dentina autóloga ofrecen un sustrato conveniente con propiedades osteoinductivas y osteogénicas óptimas para la regeneración alveolar. Objetivo: Se presenta un caso clínico de un paciente rehabilitado mediante un tratamiento quirúrgico y prostodóntico, y una actualización de la bibliografía en relación con los injertos de dentina autóloga. Caso clínico: Varón de 64 años sin antecedentes médicos ni hábitos patológicos, que presenta desgastes severos, inestabilidad oclusal y problemas estéticos. Se realiza una rehabilitación integral del paciente combinando una técnica quirúrgica de preservación alveolar con injerto de dentina autóloga, tras la cual se procede a la colocación de implantes, con un tratamiento protésico de coronas de zirconio, incrustaciones de disilicato de litio y reconstrucciones de composite. El tratamiento protésico se realiza en dos fases, pasando por una fase de provisionalización previa a la colocación de las restauraciones definitivas, empleando el flujo digital. A los 6 meses el paciente se encuentra satisfecho y con una función y estética óptima. Conclusiones: El injerto de dentina autóloga parece una alternativa eficaz y predecible como material de regeneración alveolar. Combinando esta técnica de preservación con una planificación digital, se puede maximizar el resultado del tratamiento rehabilitador, consiguiendo una mayor satisfacción del paciente. (AU)
Introduction: There are multiple procedures to achieve an adequate bone site for implant placement after teeth loss. In the last years, numerous techniques have been proposed for alveolar preservation. Dentin autologous grafts offer a convenient substrate with osteoinductive and osteogenic properties, which are optimum for alveolar regeneration. Objective: In this article, a clinical case of a patient rehabilitated by surgical and prosthodontic treatment, and a review of the literature regarding autologous dentin grafts is presented. Case report: 64 years old male, with no medical records or parafunctional habits, presents severe wear, occlusal instability and aesthetic problems. An integral rehabilitation is performed combining a surgical preservation technique with autologous dentin graft, after which the placement of the implants takes place, and a prosthodontic treatment with zirconium crowns, lithium disilicate inlays and composite restorations. The prosthodontic treatment is accomplished in two phases, going through a provisionalization phase previous to the placement of the definitive restorations, and digital workflow is used. 6 months later, the patient is satisfied, and function and aesthetic are optimum. Conclusions: Dentin autologous graft offers a predictable and effective alternative as a material for alveolar regeneration. Combining this preservation technique, with a good digital planification, results can be maximized and satisfaction for the patient can be increased. (AU)
Subject(s)
Humans , Male , Middle Aged , Dentin/surgery , Dentin/transplantation , Dentin/physiology , Bone Transplantation , RegenerationABSTRACT
The presence of third stage larvae (L3) of Anisakis spp. in wedge sole, Dicologlossa cuneata (Moreau, 1881), purchased in fishmarkets in the city of Granada (Andalusia, southern Spain) was assessed. The wedge sole were caught in two FAO zones: area 27.IXa NE Atlantic (SW Spain coast) and area 34.1.11 CE Atlantic (NW Morocco coast). Only Anisakis larvae, type I, were detected in the largest fish (>20 cm) from the CE Atlantic. These were molecularly identified as A. simplex s.s. The prevalence (P) of Anisakis in this area was 12.5% and the mean intensity (MI) was 1. The presence of Hysterothylacium spp. larvae was also detected in the fish from both areas, with the prevalence being approximately double in the CE Atlantic area (12.5 vs. 5.7). A comparison between the Anisakis-infected and non-infected fish from this area showed that the former were significantly longer than the latter (p < 0.01). These results show that Anisakis parasitization of wedge sole sold in the markets of the city of Granada is of low prevalence and intensity (P = 4.5, MI = 1), especially in those from area 27.IXa (P = 0), indicating that the risk of human infection is low, particularly as this fish is traditionally prepared by deep-frying in oil in Andalusia (southern Spain).
ABSTRACT
Familial neurodegenerative diseases commonly involve mutations that result in either aberrant proteins or dysfunctional components of the proteolytic machinery that act on aberrant proteins. UBQLN2 is a ubiquitin receptor of the UBL/UBA family that binds the proteasome through its ubiquitin-like domain and is thought to deliver ubiquitinated proteins to proteasomes for degradation. UBQLN2 mutations result in familial amyotrophic lateral sclerosis (ALS)/frontotemporal dementia in humans through an unknown mechanism. Quantitative multiplexed proteomics was used to provide for the first time an unbiased and global analysis of the role of Ubqln2 in controlling the composition of the proteome. We studied several murine models of Ubqln2-linked ALS and also generated Ubqln2 null mutant mice. We identified impacts of Ubqln2 on diverse physiological pathways, most notably serotonergic signaling. Interestingly, we observed an upregulation of proteasome subunits, suggesting a compensatory response to diminished proteasome output. Among the specific proteins whose abundance is linked to UBQLN2 function, the strongest hits were the ubiquitin ligase TRIM32 and two retroelement-derived proteins, PEG10 and CXX1B. Cycloheximide chase studies using induced human neurons and HEK293 cells suggested that PEG10 and TRIM32 are direct clients. Although UBQLN2 directs the degradation of multiple proteins via the proteasome, it surprisingly conferred strong protection from degradation on the Gag-like protein CXX1B, which is expressed from the same family of retroelement genes as PEG10. In summary, this study charts the proteomic landscape of ALS-related Ubqln2 mutants and identifies candidate client proteins that are altered in vivo in disease models and whose degradation is promoted by UBQLN2.
Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Amyotrophic Lateral Sclerosis/genetics , Autophagy-Related Proteins/genetics , Frontotemporal Dementia/genetics , Proteasome Endopeptidase Complex/metabolism , Proteomics/methods , Adaptor Proteins, Signal Transducing/deficiency , Adaptor Proteins, Signal Transducing/metabolism , Amyotrophic Lateral Sclerosis/metabolism , Amyotrophic Lateral Sclerosis/pathology , Animals , Apoptosis Regulatory Proteins/genetics , Apoptosis Regulatory Proteins/metabolism , Autophagy-Related Proteins/deficiency , Autophagy-Related Proteins/metabolism , Cell Line , Cycloheximide/pharmacology , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Disease Models, Animal , Frontotemporal Dementia/metabolism , Frontotemporal Dementia/pathology , Gene Expression Regulation , HEK293 Cells , Humans , Male , Mice , Mice, Knockout , Neurons/drug effects , Neurons/metabolism , Neurons/pathology , Protein Stability/drug effects , Proteolysis/drug effects , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Serotonin/metabolism , Signal Transduction , Trans-Activators/genetics , Trans-Activators/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolismABSTRACT
RIP1 kinase is proposed to play a critical role in driving necroptosis and inflammation in neurodegenerative disorders, including Amyotrophic Lateral Sclerosis (ALS). Preclinical studies indicated that while pharmacological inhibition of RIP1 kinase can ameliorate axonal pathology and delay disease onset in the mutant SOD1 transgenic (SOD1-Tg) mice, genetic blockade of necroptosis does not provide benefit in this mouse model. To clarify the role of RIP1 kinase activity in driving pathology in SOD1-Tg mice, we crossed SOD1-Tgs to RIP1 kinase-dead knock-in mice, and measured disease progression using functional and histopathological endpoints. Genetic inactivation of the RIP1 kinase activity in the SOD1-Tgs did not benefit the declining muscle strength or nerve function, motor neuron degeneration or neuroinflammation. In addition, we did not find evidence of phosphorylated RIP1 accumulation in the spinal cords of ALS patients. On the other hand, genetic inactivation of RIP1 kinase activity ameliorated the depletion of the neurotransmitter dopamine in a toxin model of dopaminergic neurodegeneration. These findings indicate that RIP1 kinase activity is dispensable for disease pathogenesis in the SOD1-Tg mice while inhibition of kinase activity may provide benefit in acute injury models.
Subject(s)
Amyotrophic Lateral Sclerosis/enzymology , GTPase-Activating Proteins/genetics , Motor Neurons/pathology , Superoxide Dismutase-1/genetics , Amyotrophic Lateral Sclerosis/etiology , Amyotrophic Lateral Sclerosis/pathology , Animals , Disease Models, Animal , Disease Progression , Female , HT29 Cells , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , NecroptosisABSTRACT
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by motor neuron loss that ultimately leads to fatal paralysis. Reducing levels or function of the tyrosine kinase, ephrin type-A receptor 4 (EphA4), has been suggested as a potential approach for slowing disease progression in ALS. Because EphA4 plays roles in embryonic nervous system development, study of constitutive knockout (KO) of EphA4 in mice is limited due to confounding phenotypes with homozygous knockout. We used a tamoxifen-inducible EphA4 conditional KO mouse to achieve strong reduction of EphA4 levels in postnatal mice to test for protective effects in the SOD1G93A model of ALS. We found that EphA4 KO in young mice, but not older adult mice, causes defects in muscle function, consistent with a prolonged postnatal role for EphA4 in adolescent muscle growth. When testing the effects of inducible EphA4 KO at different timepoints in SOD1G93A mice, we found no benefits on motor function or disease pathology, including muscle denervation and motor neuron loss. Our results demonstrate deleterious effects of reducing EphA4 levels in juvenile mice and do not provide support for the hypothesis that widespread EphA4 reduction is beneficial in the SOD1G93A mouse model of ALS.
Subject(s)
Amyotrophic Lateral Sclerosis/genetics , Motor Activity/genetics , Motor Neurons/pathology , Receptor, EphA4/genetics , Age Factors , Amyotrophic Lateral Sclerosis/pathology , Animals , Disease Models, Animal , Disease Progression , Mice , Mice, Transgenic , Superoxide Dismutase-1/geneticsABSTRACT
Restoration of epicardial coronary blood flow, achieved by early reperfusion with primary percutaneous coronary intervention (PPCI), is the guideline recommended to treat patients with ST-segment-elevation myocardial infarction (STEMI). However, despite successful blood restoration, increasing numbers of patients develop left ventricular adverse remodelling (LVAR) and heart failure. Therefore, reliable prognostic biomarkers for LVAR in STEMI are urgently needed. Our aim was to investigate the role of circulating microRNAs (miRNAs) and their association with LVAR in STEMI patients following the PPCI procedure. We analysed the expression of circulating miRNAs in blood samples of 56 patients collected at admission and after revascularization (at 3, 6, 12 and 24 h). The associations between miRNAs and left ventricular end diastolic volumes at 6 months were estimated to detect LVAR. miRNAs were also analysed in samples isolated from peripheral blood mononuclear cells (PBMCs) and human myocardium of failing hearts. Kinetic analysis of miRNAs showed a fast time-dependent increase in miR-133a, miR-133b, miR-193b, miR-499, and miR-320a in STEMI patients compared to controls. Moreover, the expression of miR-29a, miR-29b, miR-324, miR-208, miR-423, miR-522, and miR-545 was differentially expressed even before PPCI in STEMI. Furthermore, the increase in circulating miR-320a and the decrease in its expression in PBMCs were significantly associated with LVAR and correlated with the expression of miR-320a in human failing myocardium from ischaemic origin. In conclusion, we determined the time course expression of new circulating miRNAs in patients with STEMI treated with PPCI and we showed that miR-320a was positively associated with LVAR.
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