The role of subjective risk perception and self-esteem in the relationship between sensation seeking and aberrant behaviors on the road: A moderated-moderation model.

INTRODUCTION: Road crashes are still one of the main causes of death around the world. Risky behavior has been proposed as one of the foremost predictors, with the theoretical framework of aberrant behavior emerging as a predominant approach for its examination. Sensation seeking has been pointed out as one of the main personality predictors of aberrant behavior. The current research aimed to investigate the moderated-moderation effect of both risk perception and self-esteem in the relationship between sensation seeking and aberrant behavior. METHOD: Two studies were conducted. The first study aimed to analyze the psychometric properties of the Spanish version of the Risk Perception Scale (RPS), a 10-item self-report to assess risk perception. A sample composed of 471 Spanish drivers (319 female, Mage = 29.75) completed the RPS. In the second study, a different sample of 236 Spanish drivers (129 female, Mage = 38.49) completed a set of self-reports aiming both to analyze the concurrent and divergent validity of the RPS, and to test the main moderated-moderation hypothesis. RESULTS: With respect to the first study, the confirmatory factor analysis (CFA) supported a 7-item version which fitted in a single reliable factor (α = .74). Regarding the second study, the results supported both the concurrent and divergent validity of the RPS. Likewise, it was verified the moderated-moderation effect in the case of ordinary violations (R2 = .34), aggressive violations (R2 = .20), and lapses (R2 = .12). CONCLUSIONS: The RPS is a useful self-report to assess subjective risk perception in Spanish drivers. Both self-esteem and risk perception affect the relationship between sensation seeking and aberrant driving behavior. PRACTICAL IMPLICATIONS: Intervention programs aiming to reduce aberrant driving behavior should be focused on reducing sensation seeking tendencies while simultaneously enhancing both risk perception skills and self-esteem.

Which drivers drive as they live and who are transformed while driving? Analysis of moderators in the relationship between general anger and driving anger.

INTRODUCTION: Trait driving anger is a widely studied personality variable in the field of road safety, due to its strong relationship with both risky behavior on the road and crash-related events. The Deffenbacher's Driving Anger Scale theoretical approach has underlined different situations that could provoke anger in drivers, although trait driving anger is usually analyzed as a whole. Trait general anger has been proposed as one of the most relevant predictors of trait driving anger, showing moderate relationships with it. METHOD: The current research aimed to analyze the relationship between trait general anger and each one of the situations provoking anger, as well as to search for personality variables that could moderate these relationships. Based on literature review, it was expected that self-esteem would moderate both Discourtesy and Hostile gestures, Type-A behavior pattern would moderate both Slow driving and Traffic obstructions, and conscientiousness would moderate both Police presence and Illegal driving. A sample of 417 drivers (Mage = 31.24, SDage = 13.59, 64.5% females) taken from the Spanish general population completed a set of self-reports. RESULTS: The results showed significant moderation effects in the case of Hostile gestures, Discourtesy, Illegal driving, and Slow driving. Conditional processes of these moderations were analyzed. Lastly, practical implications are discussed, allowing for tailored interventions to be implemented based on individual drivers' tendencies. Therefore, interventions should address different triggers of driving anger: boosting self-esteem for those angered by disrespect, targeting Type-A behavior reduction for those angered by traffic slowdowns, and promoting conscientiousness enhancement for those angered by others' risky driving.

Effervescence tablets based on magnetic ionic liquids as simple microdevices for the in situ dispersive liquid-liquid microextraction of urinary biomarkers.

BACKGROUND: Magnetic ionic liquids (MILs) have been explored in dispersive liquid-liquid microextraction (DLLME). Their usage allows to substitute centrifugation and/or filtration steps by a quick magnetic separation. Besides, effervescence-assisted DLLME is one of the most known options to improve the dispersion of the extractant in the sample, while allowing to avoid the consumption of external energy during dispersion. Despite these interesting features, only one study incorporates MILs containing the tetrachloroferrate anion in effervescence tablets. These MILs are highly viscous and liquid at room temperature, thus compromising the stability of the tablets when used as extraction microdevices in effervescence-assisted DLLME, and only allowing their use in the conventional MIL-DLLME mode. RESULTS: A new class of effervescence tablets containing a Ni(II)-based MIL, that is solid at room temperature, is here proposed. This type of tablets permits their use, for first time, in the in situ DLLME mode, occurring through the transformation of a water-soluble MIL into a water-insoluble MIL microdroplet. This way, the tablet formulation included: the MIL, the metathesis reagent lithium bis[(trifluoromethyl)sulfonyl]imide, NaH2PO4 and K2CO3 as effervescence precursors salts, and Na2SO4 as salting-out and desiccating agent. The method is combined with high-performance liquid-chromatography and both fluorescence and ultraviolet detection, for the determination of monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) and benzophenones (BPs), as biomarkers in urine. The method simply involved the addition of the effervescence tablet to the sample, thus taken place simultaneously the effervescence process and the metathesis reaction, without requiring any external energy consumption. The method presented limits of detection down to 10 ng L-1 for OH-PAHs and to 0.60 µg L-1 for BPs, inter-day relative standard deviations lower than 17 %, and average relative recoveries of 94 % in urine. The determined OH-PAHs contents in urine were between 0.40 and 16 µg L-1, and between 17.8 and 334 µg L-1 for BPs. SIGNIFICANCE: We have developed the first MIL-based effervescence tablets that are completely solid, thus improving the stability and robustness of these microdevices with respect to previously reported tablets involving MILs, while permitting to perform into the in situ DLLME mode (thus gaining in extraction efficiency). This approach including the MIL-based effervescence tablets constitutes an alternative on-site platform for the analysis of urine, as satisfactory precision, accuracy, and sensitivity are achieved despite not involving any external energy input within the analytical sample preparation setup. This method also constitutes the first application of MIL-based effervescence tablets for bioanalysis.

[BMIM][X] Ionic Liquids Supported on a Pillared-Layered Metal-Organic Framework: Synthesis, Characterization, and Adsorption Properties.

Combining ionic liquids (ILs) and metal-organic frameworks (MOFs) can be an intriguing opportunity to develop advanced materials with different adsorption capabilities for environmental applications. This study reports the preparation and characterization of a 3D pillared-layered compound, namely, [Zn2(tz)2(bdc)] (CIM91), formed by 1,2,4-triazole (Htz) and 1,4-benzenedicarboxylic acid (H2bdc) ligands. Then, various loadings of the water-stable and hydrophobic IL, 1-n-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF6]), and the water-soluble 1-n-butyl-3-methylimidazolium chloride ([BMIM][Cl]) were incorporated into CIM91. Detailed characterization by X-ray powder diffraction (XRD), FT-IR spectra, scanning electron microscopy (SEM), Energy dispersive X-ray (EDX) analysis, N2 adsorption measurements, and thermogravimetric analysis confirmed the formation of [BMIM][X]/CIM91 composites and the structural stability of the MOF after the incorporation of the ionic liquids. CO2 adsorption-desorption analysis was experimentally carried out for all the materials at 298 K and 318 K, demonstrating a great enhancement in the CO2 adsorption properties of the sole MOF CIM91, particularly by including [BMIM][PF6] species in its structure with a double isosteric heat of CO2 adsorption. The composites were also tested for the adsorption of methylene blue (MB) dye. The results indicate that the incorporation of [BMIM][X] into CIM91 can substantially modify the adsorption properties of the MOF. The influence of the nature of the [BMIM][X] anions on these properties has also been analyzed.

[Pharmaceutical Interventions in Benzodiazepine users during the COVID-19 Pandemic]. / Intervenciones farmacéuticas en usuarios de benzodiacepinas durante la pandemia COVID-19.

Introduction: Pharmaceutical Intervention aims to optimize and rationalize the use, effectiveness, and safety of dispensed medications resolving drug-related problems (DRPs) and negative medicine outcomes (NMOs). Objectives: To evaluate Pharmaceutical Interventions in Benzodiazepines users during the COVID-19 pandemic from a Community Pharmacy. Method: Prospective observational, descriptive, and cross-sectional study (AEMPS code: DAA-CLO-2020-01) of Pharmaceutical Interventions offered by the community pharmacy between August 2020 and February 2021. Results: A total of 306 Pharmaceutical Interventions were conducted involving 127 patients. Health education and personalized medication information were the most common Pharmaceutical Interventions after detecting a high level of unfamiliarity with the Benzodiazepines among patients. Pharmaceutical Interventions leading to medical referrals accounted for 37.8% of the total, triggered by the detection of DRPs and/or NMOs or after identifying the patient as candidate for deprescription. These referrals included patients with a very high level of depression according to the Euroqol 5D-3L test. Pharmaceutical Interventions resulting in Medication Review with Follow-up Service were performed in 3.1% of patients. The patient acceptance rate of Pharmaceutical Interventions reached 98.4%. Conclusions: The high acceptance rate of Pharmaceutical Interventions reinforces the value of Community Pharmacy in optimizing and rationalizing Benzodiazepines usage, while strengthening the pharmacist-patient relationship. The COVID-19 pandemic posed challenges to pharmacist-physician collaboration despite of the availability of telecommunication protocols among healthcare professionals.

Risk Characterization in Patients Using Benzodiazepines While Providing Pharmaceutical Care Dispensing Service.

BACKGROUND: Tolerance and dependence stand out as the most relevant risks observed during benzodiazepine (BZD) treatments. OBJECTIVES: To evaluate the degree of dependence of patients on BZD treatments using the Tyrer test; to define a profile of patients at risk of developing BZD dependence; and to discuss the role of the pharmaceutical care offered by the community pharmacy during dispensing. METHODS: Prospective cross-sectional descriptive observational study (August 2020-February 2021) involving 127 patients using BZD. They voluntarily answered a questionnaire during the dispensing pharmaceutical care service. The study was evaluated and codified (code: DAA-CLO-2020-01) by the Spanish Agency for Drugs and Health Products (AEMPS), and statistical analysis was performed with SPSS 25.0. RESULTS: 19.05% of patients using BZD were suspected of suffering from BZD tolerance, and 77.88% of all patients were identified as being at a high risk of BZD dependence. The Tyrer test for dependence indicated a mean score of 5.59 out of 13 points. An 18-fold increased risk of developing dependence was detected in the case of coexistence of high anxiety or depression. CONCLUSIONS: The community pharmacy, through protocolized care practices and supported by tools such as the Tyrer test, can play a decisive role in the detection, prevention, and resolution of the risks associated with BZD treatments.

Integrating artificial intelligence to assess emotions in learning environments: a systematic literature review.

Introduction: Artificial Intelligence (AI) is transforming multiple sectors within our society, including education. In this context, emotions play a fundamental role in the teaching-learning process given that they influence academic performance, motivation, information retention, and student well-being. Thus, the integration of AI in emotional assessment within educational environments offers several advantages that can transform how we understand and address the socio-emotional development of students. However, there remains a lack of comprehensive approach that systematizes advancements, challenges, and opportunities in this field. Aim: This systematic literature review aims to explore how artificial intelligence (AI) is used to evaluate emotions within educational settings. We provide a comprehensive overview of the current state of research, focusing on advancements, challenges, and opportunities in the domain of AI-driven emotional assessment within educational settings. Method: The review involved a search across the following academic databases: Pubmed, Web of Science, PsycINFO and Scopus. Forty-one articles were selected that meet the established inclusion criteria. These articles were analyzed to extract key insights related to the integration of AI and emotional assessment within educational environments. Results: The findings reveal a variety of AI-driven approaches that were developed to capture and analyze students' emotional states during learning activities. The findings are summarized in four fundamental topics: (1) emotion recognition in education, (2) technology integration and learning outcomes, (3) special education and assistive technology, (4) affective computing. Among the key AI techniques employed are machine learning and facial recognition, which are used to assess emotions. These approaches demonstrate promising potential in enhancing pedagogical strategies and creating adaptive learning environments that cater to individual emotional needs. The review identified emerging factors that, while important, require further investigation to understand their relationships and implications fully. These elements could significantly enhance the use of AI in assessing emotions within educational settings. Specifically, we are referring to: (1) federated learning, (2) convolutional neural network (CNN), (3) recurrent neural network (RNN), (4) facial expression databases, and (5) ethics in the development of intelligent systems. Conclusion: This systematic literature review showcases the significance of AI in revolutionizing educational practices through emotion assessment. While advancements are evident, challenges related to accuracy, privacy, and cross-cultural validity were also identified. The synthesis of existing research highlights the need for further research into refining AI models for emotion recognition and emphasizes the importance of ethical considerations in implementing AI technologies within educational contexts.

Ubiquitin Ligase RBX2/SAG Regulates Mitochondrial Ubiquitination and Mitophagy.

BACKGROUND: Clearance of damaged mitochondria via mitophagy is crucial for cellular homeostasis. Apart from Parkin, little is known about additional Ub (ubiquitin) ligases that mediate mitochondrial ubiquitination and turnover, particularly in highly metabolically active organs such as the heart. METHODS: In this study, we have combined in silico analysis and biochemical assay to identify CRL (cullin-RING ligase) 5 as a mitochondrial Ub ligase. We generated cardiomyocytes and mice lacking RBX2 (RING-box protein 2; also known as SAG [sensitive to apoptosis gene]), a catalytic subunit of CRL5, to understand the effects of RBX2 depletion on mitochondrial ubiquitination, mitophagy, and cardiac function. We also performed proteomics analysis and RNA-sequencing analysis to define the impact of loss of RBX2 on the proteome and transcriptome. RESULTS: RBX2 and CUL (cullin) 5, 2 core components of CRL5, localize to mitochondria. Depletion of RBX2 inhibited mitochondrial ubiquitination and turnover, impaired mitochondrial membrane potential and respiration, increased cardiomyocyte cell death, and has a global impact on the mitochondrial proteome. In vivo, deletion of the Rbx2 gene in adult mouse hearts suppressed mitophagic activity, provoked accumulation of damaged mitochondria in the myocardium, and disrupted myocardial metabolism, leading to the rapid development of dilated cardiomyopathy and heart failure. Similarly, ablation of RBX2 in the developing heart resulted in dilated cardiomyopathy and heart failure. The action of RBX2 in mitochondria is not dependent on Parkin, and Parkin gene deletion had no impact on the onset and progression of cardiomyopathy in RBX2-deficient hearts. Furthermore, RBX2 controls the stability of PINK1 (PTEN-induced kinase 1) in mitochondria. CONCLUSIONS: These findings identify RBX2-CRL5 as a mitochondrial Ub ligase that regulates mitophagy and cardiac homeostasis in a Parkin-independent, PINK1-dependent manner.

Knowledge, Attitudes, and Perceptions of Skin Cancer Clinical Trials in the Hispanic Population.

OBJECTIVE: To determine the factors that might limit Hispanic patients from participating in dermatological clinical trials. METHODS: From January 2022 to July 2022, we administered a 31-item, in-person questionnaire to patients recruited in the waiting area of the Caridad Center, one of the largest free clinics in the United States with a predominately Hispanic population, and a nearby private primary care clinic. RESULTS: Overall, Hispanic patients agreed significantly more with statements in the domain of attitude and behavioral beliefs compared to non-Hispanic survey respondents. The Hispanic ethnicity was associated with increased odds of agreeing with the following statements: "My community would really benefit from skin cancer clinical trials" (OR=0.52; 95% CI 0.30, 0.92), "My participation in a skin cancer study would be very good" (OR=0.59; 95% CI 0.35, 0.99), and "I like to do good for others" (OR=0.41; 95% CI 0.22, 0.77). CONCLUSION: While the United States population is composed of 18.5% Hispanics, they only account for 1% of patients enrolled in clinical trials. This study helps identify potential motivational factors for Hispanic patients to participate in skin cancer clinical trials.

The Ubiquitin Ligase RBX2/SAG Regulates Mitochondrial Ubiquitination and Mitophagy.

Clearance of damaged mitochondria via mitophagy is crucial for cellular homeostasis. While the role of ubiquitin (Ub) ligase PARKIN in mitophagy has been extensively studied, increasing evidence suggests the existence of PARKIN-independent mitophagy in highly metabolically active organs such as the heart. Here, we identify a crucial role for Cullin-RING Ub ligase 5 (CRL5) in basal mitochondrial turnover in cardiomyocytes. CRL5 is a multi-subunit Ub ligase comprised by the catalytic RING box protein RBX2 (also known as SAG), scaffold protein Cullin 5 (CUL5), and a substrate-recognizing receptor. Analysis of the mitochondrial outer membrane-interacting proteome uncovered a robust association of CRLs with mitochondria. Subcellular fractionation, immunostaining, and immunogold electron microscopy established that RBX2 and Cul5, two core components of CRL5, localizes to mitochondria. Depletion of RBX2 inhibited mitochondrial ubiquitination and turnover, impaired mitochondrial membrane potential and respiration, and increased cell death in cardiomyocytes. In vivo , deletion of the Rbx2 gene in adult mouse hearts suppressed mitophagic activity, provoked accumulation of damaged mitochondria in the myocardium, and disrupted myocardial metabolism, leading to rapid development of dilated cardiomyopathy and heart failure. Similarly, ablation of RBX2 in the developing heart resulted in dilated cardiomyopathy and heart failure. Notably, the action of RBX2 in mitochondria is not dependent on PARKIN, and PARKIN gene deletion had no impact on the onset and progression of cardiomyopathy in RBX2-deficient hearts. Furthermore, RBX2 controls the stability of PINK1 in mitochondria. Proteomics and biochemical analyses further revealed a global impact of RBX2 deficiency on the mitochondrial proteome and identified several mitochondrial proteins as its putative substrates. These findings identify RBX2-CRL5 as a mitochondrial Ub ligase that controls mitophagy under physiological conditions in a PARKIN-independent, PINK1-dependent manner, thereby regulating cardiac homeostasis.

Post-acute pancreatitis diabetes: A complication waiting for more recognition and understanding.

Post-acute pancreatitis diabetes (PAPD) is the second most common type of diabetes below type 2 diabetes mellitus. Due to the boom in research on this entity carried out during the last decade, its recognition has increased. However, much of the medical community still does not recognize it as a medium and long-term complication of acute pancreatitis (AP). Recent prospective cohort studies show that its incidence is about 23% globally and 34.5% in patients with severe AP. With the overall increase in the incidence of AP this complication will be certainly seen more frequently. Due to its high morbidity, mortality and difficult control, early detection and treatment are essential. However, its risk factors and pathophysiological mechanisms are not clearly defined. Its diagnosis should be made excluding pre-existing diabetes and applying the criteria of the American Diabetes Association after 90 d of resolution of one or more AP episodes. This review will show the evidence published so far on the incidence and prevalence, risk factors, possible pathophysiological mechanisms, clinical outcomes, clinical characteristics and preventive and corrective management of PAPD. Some important gaps needing to be clarified in forthcoming studies will also be discussed.

Ufmylation of UFBP1 Is Dispensable for Endoplasmic Reticulum Stress Response, Embryonic Development, and Cardiac and Intestinal Homeostasis.

Protein modification by ubiquitin fold modifier 1 (UFM1), termed ufmylation, regulates various physiological and pathological processes. Among emerging UFM1 targets, UFM1 binding protein 1 (UFBP1) is the first identified ufmylation substrate. Recent clinical and animal studies have demonstrated the pivotal roles of UFBP1 in development, hematopoiesis, intestinal homeostasis, chondrogenesis, and neuronal development, which has been linked to its function in maintaining endoplasmic reticulum (ER) homeostasis. However, the importance of UFBP1 ufmylation in these cellular and physiological processes has yet to be determined. It has been proposed that ufmylation of lysine 268 (267 in humans) in UFBP1 plays a critical role in mediating the effects of the ufmylation pathway. In this study, we for the first time probe the pathophysiological significance of UFBP1 ufmylation in vivo by creating and characterizing a mouse UFBP1 knockin (KI) model in which the lysine 268 of UFBP1, the amino acid accepting UFM1, was mutated to arginine. Our results showed that the K268R mutation reduced the total ufmylated proteins without altering the expression levels of individual ufmylation enzymes in mouse embryonic fibroblasts. The K268R mutation did not alter ER stress-stimuli-induced ER stress signaling or cell death in mouse embryonic fibroblasts. The homozygous KI mice were viable and morphologically indistinguishable from their littermate wild-type controls up to one year of age. Serial echocardiography revealed no cardiac functional impairment of the homozygous KI mice. Furthermore, the homozygous KI mice exhibited the same susceptibility to dextran sulfate sodium (DSS) -induced colitis as wild-type mice. Taken together, these results suggest that UFBP1 K268 is dispensable for ER stress response, embryonic development, cardiac homeostasis under physiological conditions, and intestinal homeostasis under pathological conditions. Our studies call for future investigations to understand the biological function of UFBP1 ufmylation and offer a new mouse model to determine the roles of UFBP1 ufmylation in different tissues under stress conditions.

Quality of Life Assessment in Patients Using Benzodiazepines during the COVID-19 Pandemic in a Community Pharmacy Using EuroQol 5D-3L.

Users of benzodiazepines (BZDs) should have their quality of life monitored to minimize the risks associated with long-term treatments. The aim of this study is to use the EuroQol 5D-3L to analyze the quality of life of 127 patients under treatment with BZDs during the COVID-19 pandemic. The results show that lorazepam comprises 25.49% of all dispensing requests, and that the mean duration of BZDs treatments is four years (range: 0.3-25). When rating their general health status, BZDs users reported 59.29 points out of 100. Thirty-two percent of patients reported mobility problems; 16.5% reported having a lot of pain or discomfort despite being treated with BZDs, and 16.54% used a BZD together with an opioid analgesic. The EuroQol 5D-3L dimension "anxiety/depression" showed that, despite the use of BZDs, 48.2% of the patients reported being moderately anxious or depressed and 13.4% described themselves as very anxious or depressed. Nevertheless, 37.8% of BZDs users were identified as potential candidates to follow a BZD deprescription plan. In conclusion, BZDs users showed a low quality of life during the COVID-19 pandemic. Older patients and females have been identified as groups of patients that could benefit from integrating the use of the EuroQol 5D-3L instrument into the protocols of the pharmaceutical care follow up.

Novel Resistance Regions Carrying TnaphA6, blaVIM-2, and blaPER-1, Embedded in an ISPa40-Derived Transposon from Two Multi-Resistant Pseudomonas aeruginosa Clinical Isolates.

Antibiotic resistance is an alarming problem throughout the world and carbapenem-resistant Pseudomonas aeruginosa has been cataloged as critical in the World Health Organization list of microorganisms in urgent need for the development of new antimicrobials. In this work, we describe two novel resistance regions responsible for conferring a multidrug resistance phenotype to two clinical isolates of P. aeruginosa (Pa873 and Pa6415) obtained from patients hospitalized in the ICU of University Hospital of Uruguay. Bacterial identification and antibiotic susceptibility tests were performed using MALDI-TOF and the Vitek 2 system, respectively. WGS was performed for both isolates using Oxford Nanopore Technologies and Illumina and processed by means of hybrid assembly. Both isolates were resistant to ceftazidime, cefepime, piperacillin-tazobactam, aztreonam, and imipenem. Strain Pa6415 also showed resistance to ciprofloxacin. Both strains displayed MICs below the susceptibility breakpoint for CAZ-AVI plus 4 mg/L of aztreonam as well as cefiderocol. Both resistance regions are flanked by the left and right inverted repeats of ISPa40 in two small regions spanning 39.3 and 35.6 kb, for Pa6415 and Pa873, respectively. The resistance region of Pa6415 includes TnaphA6, and the new Tn7516 consists of IRi, In899, qacEΔ1-sul1-ISCR1, qnrVC6-ISCR1-blaPER-1-qacEΔ1-sul1, araJ-like, IS481-like tnpA, ISPa17, and IRR. On the other hand, the resistance region of Pa873 includes Tnaph6 and the new Tn7517 (IRi, In899, qacEΔ1-sul1, ISCR1-blaPER-1-qacEΔ1-sul1, araJ-like, IS481-like tnpA, ISPa17, and IRR). It is necessary to monitor the emergence of genetic structures that threaten to invalidate the available therapeutic resources.

Neddylation is required for perinatal cardiac development through stimulation of metabolic maturation.

Cardiac maturation is crucial for postnatal cardiac development and is increasingly known to be regulated by a series of transcription factors. However, post-translational mechanisms regulating this process remain unclear. Here we report the indispensable role of neddylation in cardiac maturation. Mosaic deletion of NAE1, an essential enzyme for neddylation, in neonatal hearts results in the rapid development of cardiomyopathy and heart failure. NAE1 deficiency disrupts transverse tubule formation, inhibits physiological hypertrophy, and represses fetal-to-adult isoform switching, thus culminating in cardiomyocyte immaturation. Mechanistically, we find that neddylation is needed for the perinatal metabolic transition from glycolytic to oxidative metabolism in cardiomyocytes. Further, we show that HIF1α is a putative neddylation target and that inhibition of neddylation accumulates HIF1α and impairs fatty acid utilization and bioenergetics in cardiomyocytes. Together, our data show neddylation is required for cardiomyocyte maturation through promoting oxidative metabolism in the developing heart.

Cuidados de enfermería para reducir el riesgo de hemorragia en pacientes con trombolisis por ICTUS isquémico

Objetivo: Describir las intervenciones de enfermería en pacientes con trombolisis en ictus isquémico para reducir el riesgo de hemorragia. Metodología: Investigación secundaria, revisión; integrativa. Se realizó una pregunta con la estrategia PICO: ¿Cuáles son las intervenciones de enfermería en pacientes con trombolisis en ictus isquémico para reducir el riesgo de hemorragia antes, durante y después de trombolizar al paciente? Se construyó una ecuación de búsqueda utilizando booleanos, DeCS/MeSH para facilitar la búsqueda en bases de datos. Los artículos encontrados fueron leídos críticamente y clasificados por nivel de evidencia y grados de recomendación. Estudio sin riesgo ético por ser de tipo documental. Se respetaron los derechos de autor de acuerdo con la Ley 44 de 1993. Resultados: Con las 14 unidades de análisis finales fueron construidos 3 dominios que realzan la importancia de los conocimientos y el actuar del personal de enfermería en la reducción del riesgo de hemorragia en pacientes con ictus isquémico. Dichos dominios son: 1) control y monitorización de la tensión arterial; principal cuidado de enfermería antes, durante y después de la trombolisis, 2) terapia combinada; disminución de riesgos hemorrágicos - aumento de la ventana terapéutica, 3) dosificación segura de alteplasa en situaciones contraindicadas. Conclusiones: La intervención de enfermería más significativa durante esta terapia es la monitorización y control de las cifras tensionales, debido a que su aumento mayor a 185/110 mmHg es el factor de riesgo más significativo en la aparición de hemorragias.

Objective: Describe nursing interventions in patients with thrombolysis in ischemic stroke to reduce the risk of bleeding. Methodology: Secondary research, type of review; integrative. A question was asked with the PICO strategy: What are the nursing interventions in patients with thrombolysis in ischemic stroke to reduce the risk of bleeding before, during, and after thrombolyzing the patient? A search equation was constructed using Boolean, DeCS / MeSH to facilitate database searching. The articles were critically read and classified by level of evidence and degrees of recommendation. Study without ethical risk because it is documentary type, copyright was respected according to Law 44 of 1993. Results: With the 14 final analysis units, 3 domains were constructed that highlight the importance of knowledge and the actions of the nursing staff in reducing the risk of bleeding in patients with ischemic stroke. These domains are: 1) control and monitoring of blood pressure; main nursing care before, during, and after thrombolysis, 2) combined therapy; decreased bleeding risks - increased therapeutic window, 3) safe dosage of alteplase in contraindicated situations. Conclusions: The most significant nursing intervention during this therapy is the monitoring and control of blood pressure figures, since and increase larger than 185/110 mmHg is the most significant risk factor in the appearance of bleeding.

Peptidoglycan editing in non-proliferating intracellular Salmonella as source of interference with immune signaling.

Salmonella enterica causes intracellular infections that can be limited to the intestine or spread to deeper tissues. In most cases, intracellular bacteria show moderate growth. How these bacteria face host defenses that recognize peptidoglycan, is poorly understood. Here, we report a high-resolution structural analysis of the minute amounts of peptidoglycan purified from S. enterica serovar Typhimurium (S. Typhimurium) infecting fibroblasts, a cell type in which this pathogen undergoes moderate growth and persists for days intracellularly. The peptidoglycan of these non-proliferating bacteria contains atypical crosslinked muropeptides with stem peptides trimmed at the L-alanine-D-glutamic acid-(γ) or D-glutamic acid-(γ)-meso-diaminopimelic acid motifs, both sensed by intracellular immune receptors. This peptidoglycan has a reduced glycan chain average length and ~30% increase in the L,D-crosslink, a type of bridge shared by all the atypical crosslinked muropeptides identified. The L,D-transpeptidases LdtD (YcbB) and LdtE (YnhG) are responsible for the formation of these L,D-bridges in the peptidoglycan of intracellular bacteria. We also identified in a fraction of muropeptides an unprecedented modification in the peptidoglycan of intracellular S. Typhimurium consisting of the amino alcohol alaninol replacing the terminal (fourth) D-alanine. Alaninol was still detectable in the peptidoglycan of a double mutant lacking LdtD and LdtE, thereby ruling out the contribution of these enzymes to this chemical modification. Remarkably, all multiple mutants tested lacking candidate enzymes that either trim stem peptides or form the L,D-bridges retain the capacity to modify the terminal D-alanine to alaninol and all attenuate NF-κB nuclear translocation. These data inferred a potential role of alaninol-containing muropeptides in attenuating pro-inflammatory signaling, which was confirmed with a synthetic tetrapeptide bearing such amino alcohol. We suggest that the modification of D-alanine to alaninol in the peptidoglycan of non-proliferating intracellular S. Typhimurium is an editing process exploited by this pathogen to evade immune recognition inside host cells.

Evaluation and Validation of a New Score to Measure the Severity of Small Bowel Angiodysplasia on Video Capsule Endoscopy.

INTRODUCTION: Angiodysplasias are responsible of 50% of small bowel bleeding. An endoscopic method that allows measuring its severity is not available. AIMS: The aim of the study was to validate a new endoscopic score with VCE to measure the severity of small bowel angiodysplasias (SBAD). METHODS: Four endoscopists independently reviewed VCE videos of 22 patients with SBAD. The score graded 3 variables: A - extent of lesions: E1, located in one half of the intestine and E2, in both halves; B - number of lesions: N1, <5; N2, 5-10; and N3, >10 lesions; C - probability of bleeding: P1, pale red spots; P2, bright red spots; P3, bleeding stigmata; and P4, active bleeding. Capsule Endoscopy Small Bowel Angiodysplasia Activity Index (CESBAI) was calculated as follows: E × 1 + N × 2 + P × 3. Interobserver variability was analyzed by Spearman's correlation and agreement Kappa statistic tests. RESULTS: The mean CESBAI scores by observers were O1= 11.6 ± 4.1; O2 = 11.3 ± 4.8; O3 = 11.1 ± 4.9; and O4 = 11.8 ± 4.2 (p > 0.05). Spearman's correlation values of CESBAI between every 2 observers were from 0.61 to 0.94 (p < 0.001) with a global correlation of 0.73 among all observers. Kappa values of CESBAI between every 2 observers ranged from 0.42 to 0.87 (p < 0.001) with a global agreement of 0.57 among all observers. All evaluators stated that the method was easy to use. CONCLUSIONS: CESBAI is a reliable and reproducible score. Nevertheless, these results must be validated in other studies with larger population before assessing its power for predicting bleeding recurrence.