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The association between cardiac fibrosis and galectin-3 was evaluated in patients with acute myocardial infarction (MI). The role of galectin-3 and its association with endoplasmic reticulum (ER) stress activation in the progression of cardiovascular fibrosis was also evaluated in obese-infarcted rats. The inhibitor of galectin-3 activity, modified citrus pectin (MCP; 100 mg/kg/day), and the inhibitor of the ER stress activation, 4-phenylbutyric acid (4-PBA; 500 mg/kg/day), were administered for 4 weeks after MI in obese rats. Overweight-obese patients who suffered a first MI showed higher circulating galectin-3 levels, higher extracellular volume, and LV infarcted size, as well as lower E/e'ratio and LVEF compared with normal-weight patients. A correlation was observed between galectin-3 levels and extracellular volume. Obese-infarcted animals presented cardiac hypertrophy and reduction in LVEF, and E/A ratio as compared with control animals. They also showed an increase in galectin-3 gene expression, as well as cardiac fibrosis and reduced autophagic flux. These alterations were associated with ER stress activation characterized by enhanced cardiac levels of binding immunoglobulin protein, which were correlated with those of galectin-3. Both MCP and 4-PBA not only reduced cardiac fibrosis, oxidative stress, galectin-3 levels, and ER stress activation, but also prevented cardiac functional alterations and ameliorated autophagic flux. These results show the relevant role of galectin-3 in the development of diffuse fibrosis associated with MI in the context of obesity in both the animal model and patients. Galectin-3 in tandem with ER stress activation could modulate different downstream mechanisms, including inflammation, oxidative stress, and autophagy.
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Estrés del Retículo Endoplásmico , Galectina 3 , Obesidad , Animales , Galectina 3/metabolismo , Obesidad/metabolismo , Obesidad/complicaciones , Masculino , Ratas , Humanos , Pectinas/farmacología , Persona de Mediana Edad , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Infarto del Miocardio/complicaciones , Femenino , Fibrosis , Ratas Wistar , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/patología , Fenilbutiratos/farmacología , Autofagia , Miocardio/metabolismo , Miocardio/patología , Galectinas/metabolismo , Anciano , Proteínas Sanguíneas/metabolismoRESUMEN
OBJECTIVE: To examine inequalities in self-rated health between immigrant and native populations in 2014 and 2020, and whether these inequities vary by sex/gender and social support. METHODS: This cross-sectional study used information from adults aged ≥18â¯years who participated in the European Health Interview Survey in Spain in 2014 and 2020. Self-rated health was specified as good or bad/poor. Immigration status and length of stay were considered to specify the exposure. Poisson regression was used to estimate prevalence ratios (PR) and 95% confidence intervals (CI) in each survey. Interaction terms between immigration status and survey; and immigration status, survey, and sex/gender or social support were tested. RESULTS: The adjusted analyses showed that when compared with Spanish native adults, immigrants with 6-15â¯years residing in Spain had a 1.34 (95%CI:1.18, 1.53) greater probability of rating their health as bad/poor in 2014. Similarly, these probabilities were 1.48 (95%CI:1.28, 1.75) for immigrants with 6-15â¯years residing in Spain in 2020. No heterogeneity was observed for the associations of immigrant status/length of stay with self-rated health for sex/gender or social support in either survey (p-interactions for sex/gender: 0.41 and social support: 0.71). CONCLUSION: Given the growth of the immigrant population in Spain and the importance of immigration as a social determinant of health, these findings call attention to a deeper examination of inequalities, with the aim of identifying potential factors leading to bad/poor rating of health over time.
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Physical aggression is a serious and widespread problem in society, affecting people worldwide. It impacts nearly every aspect of life. While some studies explore the root causes of violent behavior, others focus on urban planning in high-crime areas. Real-time violence detection, powered by artificial intelligence, offers a direct and efficient solution, reducing the need for extensive human supervision and saving lives. This paper is a continuation of a systematic mapping study and its objective is to provide a comprehensive and up-to-date review of AI-based video violence detection, specifically in physical assaults. Regarding violence detection, the following have been grouped and categorized from the review of the selected papers: 21 challenges that remain to be solved, 28 datasets that have been created in recent years, 21 keyframe extraction methods, 16 types of algorithm inputs, as well as a wide variety of algorithm combinations and their corresponding accuracy results. Given the lack of recent reviews dealing with the detection of violence in video, this study is considered necessary and relevant.
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Algoritmos , Aprendizaje Profundo , Grabación en Video , Violencia , Humanos , Grabación en Video/métodos , Inteligencia Artificial , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
Topological insulators are bulk insulators with metallic and fully spin-polarized surface states displaying Dirac-like band dispersion. Due to spin-momentum locking, these topological surface states (TSSs) have a predominant in-plane spin polarization in the bulk fundamental gap. Here, we show by spin-resolved photoemission spectroscopy that the TSS of a topological insulator interfaced with an antimonene bilayer exhibits nearly full out-of-plane spin polarization within the substrate gap. We connect this phenomenon to a symmetry-protected band crossing of the spin-polarized surface states. The nearly full out-of-plane spin polarization of the TSS occurs along a continuous path in the energy-momentum space, and the spin polarization within the gap can be reversibly tuned from nearly full out-of-plane to nearly full in-plane by electron doping. These findings pave the way to advanced spintronics applications that exploit the giant out-of-plane spin polarization of TSSs.
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BACKGROUND: The first waves of the COVID-19 pandemic had a negative impact on health systems and health professionals, due to the high number of cases and a lack of preparation. The aim of this study was to understand how nurses working in hospital units and in intensive care perceived the performance of nurse managers and senior hospital management during the first two waves of the pandemic. METHODS: The phenomenological approach proposed by Giorgi was used to investigate perceptions of the performance of nurse managers and senior hospital management during the first two waves of the COVID-19 pandemic in Spain. Fourteen clinical nurses who worked on the front line in inpatient units or intensive care units of the Health Services of Extremadura and Madrid in the first (March-April 2020) and second (October-November 2020) waves of the COVID-19 pandemic participated in this study. The data was collected through semi-structured interviews, following a script of themes, in a theoretical sample of nurses who were worked during the pandemic. RESULTS: Two main themes emerged from the analysis of the data: (1) perceptions about the performance of nurse managers and senior hospital managers during the first and second waves of the pandemic (health system failure; belief that senior hospital management professionals could have managed the pandemic better; recognizing the efforts of middle management (nursing supervisors); insufficient institutional support) and (2) strategies employed by nurses to compensate for the weaknesses in pandemic management. CONCLUSIONS: The clinical nurses perceived that the nurse managers demonstrated better management of the pandemic than the hospital's senior management, which they attribute to their proximity, empathy, accessibility, and ability to mediate between them and the senior management. The nurses also believe that the senior management of the hospitals was to blame for organisational failures and the poor management of the pandemic.
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PURPOSE: Assess the efficiency of a cognitive training program using an artificial intelligence application to optimize cognitive reserve and reduce memory disturbance in patients aged 55 to 75 after Class II-III elective noncardiac surgery. DESIGN: Experimental with random assignment. METHODS: The study was conducted on 80 patients undergoing surgery at the Teknon Medical Center Hospital in Barcelona, from April 2018 to June 2021. Both groups were evaluated with cognitive tests before surgery and 7 and 30 days after surgery. The experimental group was subjected to cognitive training for 10 days before surgery to improve their cognitive reserve. FINDINGS: Significant differences were found between the study groups 30 days after surgery in the three screening tests (Mini-Cog, T@M, and MFE). The intervention group presented with fewer cognitive and memory alterations. Age and pre-existing comorbidities were not correlated with an impact on memory impairment or cognitive function. CONCLUSIONS: A cognitive training program based on artificial intelligence, prescribed and monitored by anesthesia nurses has a positive impact on increasing cognitive reserve and reducing memory disturbance in patients aged 55 to 75 undergoing Class II to III elective, noncardiac surgery. This intervention may serve as a prehabilitation strategy in patients with a risk of cognitive dysfunction evaluated by anesthesia nurses for the purpose of preserving their cognitive function and optimizing their recovery.
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Procedimientos Quirúrgicos Electivos , Trastornos de la Memoria , Complicaciones Cognitivas Postoperatorias , Humanos , Femenino , Masculino , Anciano , Persona de Mediana Edad , Procedimientos Quirúrgicos Electivos/métodos , Procedimientos Quirúrgicos Electivos/efectos adversos , Complicaciones Cognitivas Postoperatorias/prevención & control , Trastornos de la Memoria/prevención & control , Disfunción Cognitiva , España , Inteligencia Artificial , Entrenamiento CognitivoRESUMEN
In this study, we assessed the potential synergistic effect of the Erns RNase activity and the poly-U insertion in the 3' untranslated region (UTR) of the low-virulence classical swine fever virus (CSFV) isolate Pinar de Rio (PdR) in innate and adaptive immunity regulation and its relationship with classical swine fever (CSF) pathogenesis in pigs. We knocked out the Erns RNase activity of PdR and replaced the long polyuridine sequence of the 3' UTR with 5 uridines found typically at this position, resulting in a double mutant, vPdR-H30K-5U. This mutant induced severe CSF in 5-day-old piglets and 3-week-old pigs, with higher lethality in the newborn (89.5%) than in the older (33.3%) pigs. However, the viremia and viral excretion were surprisingly low, while the virus load was high in the tonsils. Only alpha interferon (IFN-α) and interleukin 12 (IL-12) were highly and consistently elevated in the two groups. Additionally, high IL-8 levels were found in the newborn but not in the older pigs. This points toward a role of these cytokines in the CSF outcome, with age-related differences. The disproportional activation of innate immunity might limit systemic viral spread from the tonsils and increase virus clearance, inducing strong cytokine-mediated symptoms. Infection with vPdR-H30K-5U resulted in poor neutralizing antibody responses compared with results obtained previously with the parent and RNase knockout PdR. This study shows for the first time the synergistic effect of the 3' UTR and the Erns RNase function in regulating innate immunity against CSFV, favoring virus replication in target tissue and thus contributing to disease severity. IMPORTANCE CSF is one of the most relevant viral epizootic diseases of swine, with high economic and sanitary impact. Systematic stamping out of infected herds with and without vaccination has permitted regional virus eradication. However, the causative agent, CSFV, persists in certain areas of the world, leading to disease reemergence. Nowadays, low- and moderate-virulence strains that could induce unapparent CSF forms are prevalent, posing a challenge for disease eradication. Here, we show for the first time the synergistic role of lacking the Erns RNase activity and the 3' UTR polyuridine insertion from a low-virulence CSFV isolate in innate immunity disproportional activation. This might limit systemic viral spread to the tonsils and increase virus clearance, inducing strong cytokine-mediated symptoms, thus contributing to disease severity. These results highlight the role played by the Erns RNase activity and the 3' UTR in CSFV pathogenesis, providing new perspectives for novel diagnostic tools and vaccine strategies.
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Virus de la Fiebre Porcina Clásica , Peste Porcina Clásica , Síndrome de Liberación de Citoquinas , Regiones no Traducidas 3'/genética , Inmunidad Adaptativa/genética , Animales , Peste Porcina Clásica/inmunología , Peste Porcina Clásica/patología , Peste Porcina Clásica/virología , Virus de la Fiebre Porcina Clásica/enzimología , Virus de la Fiebre Porcina Clásica/genética , Virus de la Fiebre Porcina Clásica/inmunología , Virus de la Fiebre Porcina Clásica/patogenicidad , Síndrome de Liberación de Citoquinas/genética , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/virología , Citocinas , Inmunidad Innata/genética , Interferón-alfa/inmunología , Interleucina-12/inmunología , Ribonucleasas/genética , Ribonucleasas/metabolismo , Porcinos , Vacunas Virales , Virulencia/genéticaRESUMEN
Consensus statements have proposed the use of the National Early Warning Score 2 (NEWS2) to identify stable patients with acute pulmonary embolism (PE) and an intermediate-high risk of adverse outcomes. We aimed to externally validate NEWS2 and compare it to another predictive score (Bova). Using NEWS2 (cutoff ≥5 and ≥7) and the Bova score (cutoff >4), we classified patients as intermediate-high risk (vs. non-intermediate-high risk), and we compared the test characteristics of these risk classification tools for a complicated course within 30 days after PE diagnosis. We also assessed the validity of NEWS2 for predicting a complicated course by adding the results of echocardiography and troponin testing to the model. Of the 848 enrolled patients, the NEWS2 score ≥5 classified 471 (55.5%) and the Bova score classified 37 (4.4%) as intermediate-high risk. NEWS2 had a significantly lower specificity for a 30-day complicated course than Bova (45.4 vs. 96.3%, respectively; p < 0.001). Using the higher score threshold (≥7), the NEWS2 classified 99 (11.7%) as intermediate-high risk, and the specificity was 88.9% (difference with Bova, 7.4%; p < 0.001). The proportion of patients with intermediate-high risk PE was 2.4% for the combination of a positive troponin testing and echocardiographic right ventricle dysfunction and a positive NEWS2 (score ≥7), while the specificity was 97.8% (difference with Bova, 1.5%; p = 0.07). Bova outperforms NEWS2 for predicting a complicated course among stable patients with PE. Addition of troponin testing and echocardiography improved the specificity of NEWS2, although it was not superior to Bova. CLINICALTRIALS.GOV NUMBER: : NCT02238639.
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Puntuación de Alerta Temprana , Embolia Pulmonar , Humanos , Estudios Retrospectivos , Medición de Riesgo/métodos , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/complicaciones , TroponinaRESUMEN
Infants < 3 months with minor head trauma (MHT) are a particularly vulnerable group, though few studies have focused specifically on these patients. We aimed to evaluate the application of the PECARN prediction rule, designed for clinically important traumatic brain injury (ciTBI) in children < 2 years in infants < 3 months, and create a specific prediction rule for this population. We conducted a prospective multicenter observational study in 13 pediatric emergency departments (PEDs) in Spain. The PECARN rule was applied to all patients. A new specific prediction rule for infants < 3 months of age was created. The main outcome measures were (1) ciTBI, (2) TBI evidenced on computed tomography (CT) scan, and (3) isolated skull fracture (ISF). Telephone follow-up was conducted for all patients over the 4 weeks after the initial PED visit. Of 21,981 children with MHT, 366 (1.7%) were < 3 months old and 195 (53.3%) underwent neuroimaging, including 37 (10.1%) with CT scan. The sensitivity and negative predictive value (NPV) of the PECARN prediction rule for ciTBI were 100% (95% CI, 20.7-100) and 99.7% (95% CI, 98.4-100%), respectively. Of the 230 infants (62.8%) who met the PECARN low-risk criteria, none had ciTBI, 1 (0.4% overall, 95% CI, 0-2.4) had TBI on CT, and 2 (0.9% overall; 95% CI, 0.1-3.1) had an ISF. Among the 136 infants (37.2%) who did not meet the PECARN low-risk criteria, 1 (0.3% overall; 95% CI, 0-1.5) had ciTBI, 11 (8.1% overall; 95% CI, 4.1-14.0) had TBI on CT, and 18 (13.2% overall; 95% CI, 8-20.1) had an ISF. The sensitivity and NPV of the Spanish prediction rule for ciTBI were 100% (95% CI, 20.7-100) and 100% (95% CI, 98.4-100%), respectively. No infants in the registry developed complications during follow-up. CONCLUSION: The PECARN rule for infants < 2 years old accurately identified infants < 3 months old at low risk for ciTBI in our population, although the adapted Spanish rule presented here could be even more accurate. WHAT IS KNOWN: ⢠Infants younger than 3 months are vulnerable to minor blunt head trauma due to their age and to difficulties in assessing the subtle symptoms and minimal physical findings detected on examination. ⢠A low threshold for CT scan is recommended in this population. WHAT IS NEW: ⢠PECARN rule for infants < 2 years old is an adequate tool with which to identify infants < 3 months old at low risk for clinically important traumatic brain injury. ⢠Spanish rule could identify even more low-risk infants without overlooking important outcomes but it should be validated to confirm its predictive capacity.
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Lesiones Traumáticas del Encéfalo , Niño , Humanos , Lactante , Preescolar , Estudios Prospectivos , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Servicio de Urgencia en Hospital , Valor Predictivo de las Pruebas , Factores de EdadRESUMEN
INTRODUCTION: Germline CNVs are important contributors to hereditary cancer. In genetic diagnostics, multiplex ligation-dependent probe amplification (MLPA) is commonly used to identify them. However, MLPA is time-consuming and expensive if applied to many genes, hence many routine laboratories test only a subset of genes of interest. METHODS AND RESULTS: We evaluated a next-generation sequencing (NGS)-based CNV detection tool (DECoN) as first-tier screening to decrease costs and turnaround time and expand CNV analysis to all genes of clinical interest in our diagnostics routine. We used DECoN in a retrospective cohort of 1860 patients where a limited number of genes were previously analysed by MLPA, and in a prospective cohort of 2041 patients, without MLPA analysis. In the retrospective cohort, 6 new CNVs were identified and confirmed by MLPA. In the prospective cohort, 19 CNVs were identified and confirmed by MLPA, 8 of these would have been lost in our previous MLPA-restricted detection strategy. Also, the number of genes tested by MLPA across all samples decreased by 93.0% in the prospective cohort. CONCLUSION: Including an in silico germline NGS CNV detection tool improved our genetic diagnostics strategy in hereditary cancer, both increasing the number of CNVs detected and reducing turnaround time and costs.
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Variaciones en el Número de Copia de ADN , Detección Precoz del Cáncer , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Neoplasias/genética , Programas Informáticos , Costos y Análisis de Costo , Predisposición Genética a la Enfermedad , Pruebas Genéticas/economía , Pruebas Genéticas/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/economía , Humanos , Mutación , Neoplasias/congénito , Neoplasias/diagnóstico , Estudios Prospectivos , Estudios Retrospectivos , Análisis de Secuencia de ADN/economía , Análisis de Secuencia de ADN/métodosRESUMEN
AIM: To determine the percentage of change and increment in glucose levels after a normal oral glucose tolerance test between 24 and 28 weeks of pregnancy. METHODS: We studied 3510 pregnant women who attended their obstetric delivery at a tertiary care hospital in Guadalajara, Mexico in 2018, according to characteristics and risk 1647 (47%) patients were screened for diabetes diagnosis using the oral glucose tolerance test, 501 patients reported normal values between their 24th and 28th week of pregnancy, only 400 patients had their fasting glucose level measured on the same day of their obstetric delivery, to be compared. RESULTS: Average age was 30 years, with an average of 25.3 weeks of pregnancy. The fasting serum glucose levels taken after 28 weeks of pregnancy and before the obstetrical delivery showed an increase of 1.1 mmol/L in women who develop gestational diabetes mellitus, in contrast to women who did not develop gestational diabetes mellitus after 28 weeks their blood glucose only increased on average 0.4 mmol/L. The incidence of gestational diabetes mellitus in the study population during 2018 was 32.7%. Patients who developed gestational diabetes mellitus after a normal oral glucose tolerance test had greater body mass index before the pregnancy and newborns had a higher weight than babies born to mothers without gestational diabetes mellitus. CONCLUSION: Changes in glucose levels after the oral tolerance test of normal glucose require strict monitoring, in that it was demonstrated that 3% of patients developed gestational diabetes mellitus after week 28 of gestation.
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Diabetes Gestacional , Embarazo , Femenino , Humanos , Recién Nacido , Adulto , Glucemia , Prueba de Tolerancia a la Glucosa , Parto , MéxicoRESUMEN
Transcranial direct current stimulation (tDCS) can influence performance on behavioral tasks and improve symptoms of brain conditions. Yet, it remains unclear precisely how tDCS affects brain function and connectivity. Here, we measured changes in functional connectivity (FC) metrics in blood-oxygenation-level-dependent (BOLD) fMRI data acquired during MR-compatible tDCS in a whole-brain analysis with corrections for false discovery rate. Volunteers (n = 64) received active tDCS, sham tDCS, and rest (no stimulation), using one of three previously established electrode tDCS montages targeting left dorsolateral prefrontal cortex (DLPFC, n = 37), lateral temporoparietal area (LTA, n = 16), or superior temporal cortex (STC, n = 11). In brain networks where simulated E field was highest in each montage, connectivity with remote nodes decreased during active tDCS. During active DLPFC-tDCS, connectivity decreased between a fronto-parietal network and subgenual ACC, while during LTA-tDCS connectivity decreased between an auditory-somatomotor network and frontal operculum. Active DLPFC-tDCS was also associated with increased connectivity within an orbitofrontal network overlapping subgenual ACC. Irrespective of montage, FC metrics increased in sensorimotor and attention regions during both active and sham tDCS, which may reflect the cognitive-perceptual demands of tDCS. Taken together, these results indicate that tDCS may have both intended and unintended effects on ongoing brain activity, stressing the importance of including sham, stimulation-absent, and active comparators in basic science and clinical trials of tDCS.
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Imagen por Resonancia Magnética/métodos , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiología , Estimulación Transcraneal de Corriente Directa/métodos , Adulto , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , MasculinoRESUMEN
Netrin 1 (Ntn1) is a cell migration protein with an anti-inflammatory effect, which may play a key role in the pathological development of type 2 diabetes (T2D). In this study, we evaluate the relationships between the serum concentrations of Ntn1, glucose, and high-sensitivity C-reactive Protein (hsCRP). We carried out a cross-sectional study including 90 individuals divided into three groups (n = 30): healthy subjects, individuals with obesity without glucose alterations, and individuals with newly diagnosed T2D. Serum concentrations of Ntn1 and hs-CRP were determined by enzyme-linked immunosorbent assay (ELISA). The serum concentration of Ntn1 was higher in individuals with newly diagnosed T2D (0.33 ± 0.22 ng/mL), in comparison to healthy subjects and individuals with obesity (0.13 ± 0.06 and 0.15 ± 0.07 ng/mL, respectively). In addition, we observed a positive association between the levels of Ntn1 and hsCRP (rho = 0.443; p < 0.001) as well as with serum glucose (rho = −0.110; p = 0.05). The serum concentration of Ntn1 was higher in individuals with T2D, in comparison with the other groups in this study, and presented a positive correlation with hsCRP. Therefore, Ntn1 can be considered a promising risk biomarker and a potential therapeutic target for T2D.
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Hepatitis C virus (HCV) infection triggers Golgi fragmentation through the Golgi-resident protein immunity-related GTPase M (IRGM). Here, we report the roles of NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) and ASC (apoptosis-associated speck-like protein containing a caspase activation and recruitment domain [CARD]), two inflammasome components, in the initial events leading to this fragmentation. We show that ASC resides at the Golgi with IRGM at homeostasis. Upon infection, ASC dissociates from both IRGM and the Golgi and associates with HCV-induced NLRP3. NLRP3 silencing inhibits Golgi fragmentation. ASC silencing disrupts the Golgi structure in both control and infected cells and reduces the localization of IRGM at the Golgi. IRGM depletion in the ASC-silenced cells cannot totally restore the Golgi structure. These data highlight a role for ASC, upstream of the formation of the inflammasome, in regulating IRGM through its control on the Golgi. A similar mechanism occurs in response to nigericin treatment, but not in cells infected with another member of the Flaviviridae family, Zika virus (ZIKV). We propose a model for a newly ascribed function of the inflammasome components in Golgi structural remodeling during certain stimuli.IMPORTANCE Numerous pathogens can affect cellular homeostasis and organelle dynamics. Hepatitis C virus (HCV) triggers Golgi fragmentation through the immunity-related GTPase M (IRGM), a resident Golgi protein, to enhance its lipid supply for replication. Here, we reveal the role of the inflammasome components NLRP3 and ASC in this process, thus uncovering a new interplay between effectors of inflammation and viral infection or stress. We show that the inflammasome component ASC resides at the Golgi under homeostasis and associates with IRGM. Upon HCV infection, ASC is recruited to NLRP3 and dissociates from IRGM, causing Golgi fragmentation. Our results uncover that aside from their known function in the inflammation response, these host defense regulators also ensure the maintenance of intact intracellular structure in homeostasis, while their activation relieves factors leading to Golgi remodeling.
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Proteínas Adaptadoras de Señalización CARD/metabolismo , Proteínas de Unión al GTP/metabolismo , Aparato de Golgi/fisiología , Hepacivirus/aislamiento & purificación , Hepatitis C/virología , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Apoptosis , Proteínas Adaptadoras de Señalización CARD/genética , Proteínas de Unión al GTP/genética , Aparato de Golgi/virología , Hepatitis C/metabolismo , Hepatitis C/patología , Humanos , Proteína con Dominio Pirina 3 de la Familia NLR/genéticaRESUMEN
BACKGROUND: For patients with suspected pulmonary embolism (PE), age- or clinically-adjusted D-dimer threshold level can be used to define a negative test that safely excludes PE and reduces the use of imaging. However, the utility of this approach in patients hospitalized for chronic obstructive pulmonary disease (COPD) exacerbation is undefined. METHODS: We ran an analysis of the patients hospitalized for COPD exacerbation and randomized to the intervention in the SLICE trial. Using the conventional strategy as the reference, we compared the proportion of patients with a negative D-dimer result, and the negative predictive value and sensitivity of three D-dimer threshold strategies for initial PE or subsequent diagnosis of venous thromboembolism (VTE): the age-adjusted strategy, the Wells-adjusted strategy, and the YEARS-adjusted strategy. RESULTS: We included 368 patients. Using a conventional threshold, 182 (49.5%) patients had negative D-dimer values, of whom 1 (0.6%) had PE (sensitivity, 94.1%). The use of an age-adjusted threshold increased the number of patients in whom PE could be excluded from 182 to 233 patients (63.3%), and the proportion of false-negative findings increased from 0.5% to 1.7% (sensitivity, 76.5%). With the use of the Wells or YEARS strategies, 64.4% and 71.5% had negative values, and the proportion of false-negative findings was 2.5% (sensitivity, 64.7%) and 2.7% (sensitivity, 58.8%), respectively. CONCLUSIONS: In patients hospitalized for COPD exacerbation, compared with the conventional strategy, age- or clinically-adjusted strategies of D-dimer interpretation were associated with a larger proportion of patients in whom PE was ruled out with a higher failure rate. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT02238639 .
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Specific knowledge of the features of minor head trauma in infants is necessary to develop appropriate preventive strategies and adjust clinical management in pediatric emergency departments (PEDs). The aim of this study is to describe the epidemiology of minor blunt head trauma in infants < 3 months who present to PEDs. We performed a prospective study of infants evaluated in any of 13 Spanish PEDs within 24 h of a minor head trauma (Glasgow Coma Scale scores of 14-15) between May 2017 and November 2020. Telephone follow-up was conducted for all patients over the 4 weeks after the initial PED visit. Of 1,150,255 visits recorded, 21,981 children (1.9%) sustained a head injury, 386 of whom (0.03%) were under 3 months old. Among the 369 patients who met the inclusion criteria (0.03%), 206 (56.3%) were male. The main causes of trauma were fall-related (298; 80.8%), either from furniture (138/298; 46.3%), strollers (92/298; 30.9%), or a caregiver's arms (61/298; 20.5%). Most infants were asymptomatic (317; 85.9%) and showed no signs of injury on physical exam (210; 56.9%). Imaging studies were performed in 195 patients (52.8%): 37 (10.0%) underwent computed tomography (CT) scan, 162 (43.9%) X-ray, and 22 (6.0%) ultrasound. A clinically important traumatic brain injury (ciTBI) occurred in 1 infant (0.3% overall; 95% CI, 0-1.5), TBI was evidenced on CT scan in 12 (3.3% overall; 95% CI, 1.7-5.7), and 20 infants had an isolated skull fracture (5.5% overall; 95% CI, 3.4-8.3). All outcomes were caused by falls onto hard surfaces. CONCLUSION: Most head injuries in infants younger than 3 months are benign, and the rate of ciTBI is low. Prevention strategies should focus on falls onto hard surfaces from furniture, strollers, and caregivers' arms. Optimizing imaging studies should be a priority in this population. WHAT IS KNOWN: ⢠Infants younger than 3 months are vulnerable to minor blunt head trauma due to their age and to difficulties in assessing the subtle symptoms and minimal physical findings detected on examination. ⢠A low threshold for CT scan is recommended in this population. WHAT IS NEW: ⢠Most cases of blunt head trauma in infants younger than 3 months have good outcomes, and the rate of clinically important traumatic brain injury is low. ⢠Optimizing imaging studies should be a priority in this population, avoiding X-ray examinations and reducing unnecessary CT scans.
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Lesiones Traumáticas del Encéfalo , Traumatismos Cerrados de la Cabeza , Niño , Servicio de Urgencia en Hospital , Femenino , Escala de Coma de Glasgow , Traumatismos Cerrados de la Cabeza/diagnóstico , Traumatismos Cerrados de la Cabeza/epidemiología , Traumatismos Cerrados de la Cabeza/etiología , Humanos , Lactante , Recién Nacido , Masculino , Estudios ProspectivosRESUMEN
Type I restriction-modification (R-M) systems consist of a DNA endonuclease (HsdR, HsdM and HsdS subunits) and methyltransferase (HsdM and HsdS subunits). The hsdS sequences flanked by inverted repeats (referred to as epigenetic invertons) in certain Type I R-M systems undergo invertase-catalyzed inversions. Previous studies in Streptococcus pneumoniae have shown that hsdS inversions within clonal populations produce subpopulations with profound differences in the methylome, cellular physiology and virulence. In this study, we bioinformatically identified six major clades of the tyrosine and serine family invertases homologs from 16 bacterial phyla, which potentially catalyze hsdS inversions in the epigenetic invertons. In particular, the epigenetic invertons are highly enriched in host-associated bacteria. We further verified hsdS inversions in the Type I R-M systems of four representative host-associated bacteria and found that each of the resultant hsdS allelic variants specifies methylation of a unique DNA sequence. In addition, transcriptome analysis revealed that hsdS allelic variations in Enterococcus faecalis exert significant impact on gene expression. These findings indicate that epigenetic switches driven by invertases in the epigenetic invertons broadly operate in the host-associated bacteria, which may broadly contribute to bacterial host adaptation and virulence beyond the role of the Type I R-M systems against phage infection.
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Proteínas Bacterianas/genética , Enzimas de Restricción-Modificación del ADN/genética , Epigénesis Genética , Regulación Bacteriana de la Expresión Génica , Bacteroides fragilis/genética , Metilación de ADN , ADN Bacteriano/química , Enterococcus faecalis/genética , Secuencias Invertidas Repetidas , Streptococcus agalactiae/genética , Treponema denticola/genéticaRESUMEN
Melanin-concentrating hormone (MCH) is a 19aa cyclic peptide exclusively expressed in the lateral hypothalamic area, which is an area of the brain involved in a large number of physiological functions and vital processes such as nutrient sensing, food intake, sleep-wake arousal, memory formation, and reproduction. However, the role of the lateral hypothalamic area in metabolic regulation stands out as the most relevant function. MCH regulates energy balance and glucose homeostasis by controlling food intake and peripheral lipid metabolism, energy expenditure, locomotor activity and brown adipose tissue thermogenesis. However, the MCH control of energy balance is a complex mechanism that involves the interaction of several neuroendocrine systems. The aim of the present work is to describe the current knowledge of the crosstalk of MCH with different endocrine factors. We also provide our view about the possible use of melanin-concentrating hormone receptor antagonists for the treatment of metabolic complications. In light of the data provided here and based on its actions and function, we believe that the MCH system emerges as an important target for the treatment of obesity and its comorbidities.
Asunto(s)
Hormonas Hipotalámicas/metabolismo , Melaninas/metabolismo , Sistemas Neurosecretores/metabolismo , Obesidad/metabolismo , Hormonas Hipofisarias/metabolismo , Animales , Metabolismo Energético , Humanos , Área Hipotalámica Lateral/metabolismo , Metabolismo de los LípidosRESUMEN
Automatic prediction of the aesthetic value of images has received increasing attention in recent years. This is due, on the one hand, to the potential impact that predicting the aesthetic value has on practical applications. Even so, it remains a difficult task given the subjectivity and complexity of the problem. An image aesthetics assessment system was developed in recent years by our research group. In this work, its potential to be applied in commercial tasks is tested. With this objective, a set of three portals and three real estate agencies in Spain were taken as case studies. Images of their websites were taken to build the experimental dataset and a validation method was developed to test their original order with another proposed one according to their aesthetic value. So, in this new order, the images that have the high aesthetic score by the AI system will occupy the first positions of the portal. Relevant results were obtained, with an average increase of 52.54% in the number of clicks on the ads, in the experiment with Real Estate portals. A statistical analysis prove that there is a significant difference in the number of clicks after selecting the images with the AI system.
RESUMEN
Low-virulence classical swine fever virus (CSFV) strains make CSF eradication particularly difficult. Few data are available on the molecular determinants of CSFV virulence. The aim of the present study was to assess a possible role for CSFV virulence of a unique, uninterrupted 36-uridine (poly-U) sequence found in the 3' untranslated region (3' UTR) of the low-virulence CSFV isolate Pinar de Rio (PdR). To this end, a pair of cDNA-derived viruses based on the PdR backbone were generated, one carrying the long poly-U insertion in the 3' UTR (vPdR-36U) and the other harboring the standard 5 uridines at this position (vPdR-5U). Two groups of 20 5-day-old piglets were infected with vPdR-36U and vPdR-5U. Ten contact piglets were added to each group. Disease progression, virus replication, and immune responses were monitored for 5 weeks. The vPdR-5U virus was significantly more virulent than the vPdR-36U virus, with more severe disease, higher mortality, and significantly higher viral loads in serum and body secretions, despite similar replication characteristics in cell culture. The two viruses were transmitted to all contact piglets. Ninety percent of the piglets infected with vPdR-36U seroconverted, while only one vPdR-5U-infected piglet developed antibodies. The vPdR-5U-infected piglets showed only transient alpha interferon (IFN-α) responses in serum after 1 week of infection, while the vPdR-36U-infected piglets showed sustained IFN-α levels during the first 2 weeks. Taken together, these data show that the 3' UTR poly-U insertion acquired by the PdR isolate reduces viral virulence and activates the innate and humoral immune responses without affecting viral transmission.IMPORTANCE Classical swine fever (CSF), a highly contagious viral disease of pigs, is still endemic in some countries of Asia and Central and South America. Considering that the 3' untranslated region (3' UTR) plays an important role in flavivirus replication, the present study showed for the first time that a long polyuridine sequence acquired in the 3' UTR by an endemic CSFV isolate can activate immunity, control viral replication, and modulate disease in piglets. Our findings provide new avenues for the development of novel vaccines against infections with CSF virus and other flaviviruses. Knowledge of molecular virulence determinants is also relevant for future development of rapid and efficient diagnostic tools for the prediction of the virulence of field isolates and for efficient CSF control.