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El objetivo de esta investigación es analizar las experiencias de los alumnos de la carrera de Ingeniería en Gestión Industrial en el uso de herramienta tecnológica en manejo de inventarios a manera de intervención didáctica, con la finalidad de que experimenten dentro de su formación utilizar software reales utilizados en la industria con el propósito de enriquecer la futura práctica pedagógica. El enfoque usado fue cuantitativo, con la participación de 48 estudiantes distribuidos en dos grupos 24 de cada uno (mismo semestre, distinto docente). Los estudiantes reportaron mayor sensación de acompañamiento con la incorporación de la variable en la intervención didáctica, a pesar de algunos problemas en las habilidades tecnológicas. Estos resultados serán muy útiles en el diseño adecuado de elementos tecnológicos para el desarrollo de cada asignatura como resultado de la detección de áreas de mejora en la infraestructura tecnológica, en la capacitación docente y en la formación de los estudiantes.

Este texto busca mostrar los aspectos destacados de tres obras relacionadas con la divulgación de la ciencia, especialmente de química, escritas por Alejandro Navarro.

Esta editorial se enfoca en los dos artículos presentes en este número, uno dedicado al uso de robots que hacen uso de herramientas de inteligencia artificial para la síntesis de fármacos, y el segundo centrado en las características especiales de las partículas Janus, que pueden autopropulsarse en determinadas condiciones.

Background Cytochrome P450 2C19 (CYP2C19) intermediate and poor metabolizer patients exhibit diminished clopidogrel clinical effectiveness after percutaneous coronary intervention (PCI). However, outcome studies to date have lacked racial diversity. Thus, the impact of CYP2C19 genotype on cardiovascular outcomes in patients treated with clopidogrel who identify as Black or African American remains unclear. Methods and Results Adults among 5 institutions who self‐identified as Black or African American, underwent PCI and clinical CYP2C19 genotyping, and were treated with clopidogrel were included. Data were abstracted from health records. Major atherothrombotic (composite of death, myocardial infarction, ischemic stroke, stent thrombosis, or revascularization for unstable angina) and bleeding event rates within 1 year after PCI were compared across CYP2C19 metabolizer groups using multivariable Cox regression adjusted for potential confounders and baseline variables meeting a threshold of P

Abstract The present paper presents the analytical study of an unusual Peruvian 1899 dinero coin whose authenticity has been questioned since the 1970’s. This coin, which is present in some numismatic collections although there is no record of having been minted officially, has been characterized using non-destructive techniques such as X-ray fluorescence (XRF), scanning electron microscopy coupled with energy dispersive spectroscopy (SEM–EDS), and X-ray diffraction (XRD). Results are consistent with a cast counterfeit coin made at the turn of the 19th and 20th using a copper base alloy that was silver-platted to pass unnoticed among the public. The alloy used, generally known as german silver, was common for counterfeits in North America and Europe in that period. The historical reasons for the appearance of this unexpected coin in Peru during a time of economic difficulties, where the public experienced a shortage of small-change coins, are briefly outlined.

Esta editorial se centra en el principal problema ético que ha sacudido el ámbito de la investigación científica en el Perú: la compra de autorías en publicaciones por pseudocientíficos que buscan engañar tanto a sus empleadores, lectores y estudiantes, con hojas de vida falsas en infladas. Estas graves faltas de ética sientan un pésimo ejemplo a los jóvenes investigadores y dañan la integridad científica.

Abstract Aims Inhibitors of SGLT2 (SGLT2i) have shown a positive impact in patients with chronic heart failure and reduced ejection fraction (HFrEF). Nonetheless, the direct effects of SGLT2i on cardiac cells and how their association with main drugs used for HFrEF affect the behaviour and signalling pathways of myocardial fibroblasts are still unknown. We aimed to determine the effects of dapagliflozin alone and in combination with sacubitril/valsartan (LCZ696) or spironolactone on the function of myocardial fibroblasts of patients with heart failure and reduced ejection fraction (HFrEF). Methods and results Myocardial fibroblasts isolated from HFrEF patients (n = 5) were treated with dapagliflozin alone (1 nM–1 μM) or combined with LCZ696 (100 nM) or spironolactone (100 nM). The migratory rate was determined by wound‐healing scratch assay. Expression of heart failure (HF) markers and signalling pathways activation were analysed with multiplexed protein array. Commercially available cardiac fibroblasts from healthy donors were used as Control (n = 4). Fibroblasts from HFrEF show higher migratory rate compared with control (P = 0.0036), and increased expression of HF markers [fold‐change (Log2): COL1A1–1.3; IL‐1b–1.9; IL‐6–1.7; FN1–2.9 (P

Resumen de los aspectos más destacados del libro “la Química del Dinero” de Brian Rohrig.

Esta editorial se centra en los dos artículos publicados en el número 1 del volumen 37 de 2023: el primero nos descubre las enormes potencialidades de la química bioortogonal usando nanomateriales mientras que el segundo es un estudio donde se exponen las posibles rutas hacia sustitutos menos contaminantes del combustible diésel.

Predictive biomarkers of trabectedin represent an unmet need in advanced soft‐tissue sarcomas (STS). DNA damage repair (DDR) genes, involved in homologous recombination or nucleotide excision repair, had been previously described as biomarkers of trabectedin resistance or sensitivity, respectively. The majority of these studies only focused on specific factors (ERCC1, ERCC5, and BRCA1) and did not evaluate several other DDR‐related genes that could have a relevant role for trabectedin efficacy. In this retrospective translational study, 118 genes involved in DDR were evaluated to determine, by transcriptomics, a predictive gene signature of trabectedin efficacy. A six‐gene predictive signature of trabectedin efficacy was built in a series of 139 tumor samples from patients with advanced STS. Patients in the high‐risk gene signature group showed a significantly worse progression‐free survival compared with patients in the low‐risk group (2.1 vs 6.0 months, respectively). Differential gene expression analysis defined new potential predictive biomarkers of trabectedin sensitivity (PARP3 and CCNH) or resistance (DNAJB11 and PARP1). Our study identified a new gene signature that significantly predicts patients with higher probability to respond to treatment with trabectedin. Targeting some genes of this signature emerges as a potential strategy to enhance trabectedin efficacy.

Resumen y recomendación del libro “Por qué creemos en mierdas. Cómo nos engañamos a nosotros mismos”.

Background Long‐term outcomes of ST‐segment–elevation myocardial infarction in patients with diabetes have been barely investigated. The objective of this analysis from the EXAMINATION‐EXTEND (10‐Years Follow‐Up of the EXAMINATION trial) trial was to compare 10‐year outcomes of patients with ST‐segment–elevation myocardial infarction with and without diabetes. Methods and Results Of the study population, 258 patients had diabetes and 1240 did not. The primary end point was patient‐oriented composite end point of all‐cause death, any myocardial infarction, or any revascularization. Secondary end points were the individual components of the primary combined end point, cardiac death, target vessel myocardial infarction, target lesion revascularization, and stent thrombosis. All end points were adjusted for potential confounders. At 10 years, patients with diabetes showed a higher incidence of patient‐oriented composite end point compared with those without (46.5% versus 33.0%; adjusted hazard ratio [HR], 1.31 [95% CI, 1.05–1.61]; P=0.016) mainly driven by a higher incidence of any revascularization (24.4% versus 16.6%; adjusted HR, 1.61 [95% CI, 1.19–2.17]; P=0.002). Specifically, patients with diabetes had a higher incidence of any revascularization during the first 5 years of follow‐up (20.2% versus 12.8%; adjusted HR, 1.57 [95% CI, 1.13–2.19]; P=0.007) compared with those without diabetes. No statistically significant differences were found with respect to the other end points. Conclusions Patients with ST‐segment–elevation myocardial infarction who had diabetes had worse clinical outcome at 10 years compared with those without diabetes, mainly driven by a higher incidence of any revascularizations in the first 5 years. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04462315.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive neoplasm with very poor patient survival outcomes despite available treatments. There is an urgent need for new potential treatment options and novel biomarkers for these patients. Delta-like canonical Notch ligand 3 (DLL3) interacts with the Notch receptor and causes inhibition of Notch signaling, which confers a survival advantage to PDAC cells. Thus, DLL3 expression could affect cell survival, and its inhibition could increase a patient’s survival. To test this hypothesis, a survival analysis was conducted using the progression-free and overall survival from two independent datasets of PDAC patients, with one using mRNA z-score levels and the other using the Hscore protein expression level; both were carried out using a log-rank test and plotted using Kaplan–Meier curves. DLL3 at the mRNA expression level showed an association between high mRNA expression and both a longer progression-free survival (PFS) and overall survival (OS) of patients. Then, we designed a retrospective study with resected PDAC samples. Our primary objective with this dataset was to assess the relationship between PFS and OS and DLL3 protein expression. The secondary assessment was to provide a rationale for the use of anti-DLL3-based treatments in combination with immunotherapy that is supported by the link between DLL3 and other factors that are involved in immune checkpoints. The survival analyses revealed a protective effect of high DLL3 protein expression levels in both PFS and OS. Interestingly, high DLL3 protein expression levels were significantly correlated with PD-L1/2 and negatively correlated with NOTCH1. Therefore, DLL3 could be considered a biomarker for better prognosis in resectable PDAC patients as well as a therapeutic biomarker for immunotherapy response. These facts set a rationale for testing anti-DLL3-based treatments either alone or combined with immunotherapy or other NOTCH1 inhibitors.

Abstract Background Participatory research offers a promising approach to addressing health inequities and improving the social determinants of health for diverse populations of adolescents. However, little research has systematically explored factors influencing the implementation of participatory health interventions targeting health disparities. Objective This study examined the utility of the Consolidated Framework for Implementation Research (CFIR) in identifying and comparing barriers and facilitators influencing implementation of participatory research trials by employing an adaptation of the CFIR to assess the implementation of a multi-component, urban public school-based participatory health intervention. Methods We collected qualitative data over a one-year period through weekly team meeting observational field notes and regular semi-structured interviews with five community-based participatory researchers, one school-based partner, and four school principals involved in implementing a participatory intervention in five schools. Adapted CFIR constructs guided our largely deductive approach to thematic data analysis. We ranked each of the three intervention components as high or low implementation to create an overall implementation effectiveness score for all five schools. Cross-case comparison of constructs across high and low implementation schools identified constructs that most strongly influenced implementation. Results Ten of 30 assessed constructs consistently distinguished between high and low implementation schools in this participatory intervention, with five strongly distinguishing. Three additional constructs played influential, though non-distinguishing, roles within this participatory intervention implementation. Influential constructs spanned all five domains and fit within three broad themes: 1) leadership engagement, 2) alignment between the intervention and institutional goals, priorities, demographics, and existing systems, and 3) tensions between adaptability and complexity within participatory interventions. However, the dynamic and collaborative nature of participatory intervention implementation underscores the artificial distinction between inner and outer settings in participatory research and the individual behavior change focus does not consider how relationships between stakeholders at multiple levels of participatory interventions shape the implementation process. Conclusions The CFIR is a useful framework for the assessment of participatory research trial implementation. Our findings underscore how the framework can be readily adapted to further strengthen its fit as a tool to examine project implementation in this context.

ABSTRACT Ischemic heart disease is the most common cause of death worldwide. In patients with ST-segment elevation myocardial infarction (STEMI), optimizing primary percutaneous coronary intervention is crucial to improve prognosis. Over the years, many studies have been published on the value of second-generation stents, strategies to reduce myocardial damage, how to achieve complete revascularization and also on percutaneous mechanical circulatory support devices, which all are attractive therapeutic options to treat patients with STEMI complicated by cardiogenic shock. In this review we will be discussing how primary percutaneous coronary intervention can be optimized with respect to stent selection and revascularization strategy to reduce myocardial damage and improve clinical outcomes. In addition, we review published data on the use of mechanical circulatory support devices in patients with STEMI complicated by cardiogenic shock.

RESUMEN La cardiopatía isquémica es la causa más común de mortalidad en todo el mundo. En pacientes con infarto agudo de miocardio con elevación del segmento ST (IAMCEST), la optimización de la intervención coronaria percutánea primaria es crucial para mejorar el pronóstico. Durante estos últimos años se han publicado muchos estudios sobre el valor de los stents de segunda generación, sobre estrategias para reducir el daño miocárdico, sobre cómo conseguir la revascularización completa y sobre dispositivos de apoyo circulatorio mecánico percutáneo que representan una opción terapéutica atractiva en pacientes con IAMCEST complicado con shock cardiogénico. En esta revisión se discute cómo se puede optimizar la intervención coronaria percutánea primaria con respecto a la selección de los stents y la estrategia de revascularización, con el fin de reducir el daño miocárdico y mejorar los resultados clínicos. Además, se revisan los datos publicados sobre el uso de dispositivos de apoyo circulatorio mecánico en pacientes con IAMCEST complicado por shock cardiogénico.

The vast majority of patients with soft tissue sarcomas (STS) of the trunk and bilateral lung metastases at diagnosis are considered incurable. These tumors have poor prognosis as only a palliative therapeutic approach can be offered to patients. We report on an extremely rare case in which bilateral lung metastases disappeared spontaneously following surgical resection of the primary CIC-rearranged sarcoma with no addition of chemotherapy or any other systemic therapy. A 53-year-old female presented with a rapidly swelling mass on her back. A magnetic resonance imaging scan of the chest revealed a large soft tissue mass on the posterior chest wall and bilateral lung metastases. Soon after stereotactic core-needle biopsy confirmation of round-cell sarcoma, the patient underwent surgery of the primary tumor as it started to be increasingly symptomatic. The resected specimen was pathologically diagnosed a poorly differentiated grade 3 sarcoma. Approximately 1 month later, a new CT scan revealed that the lung metastases were smaller and some of them had completely disappeared. Shortly afterward, the patient started adjuvant external beam radiotherapy of the tumor bed for 14 months. During the last follow-up visit, the patient confirmed no evidence of disease for 35 months postoperatively. In parallel, a histological study of pulmonary nodules, molecular analyses of the tumor, and a comprehensive study of the patient’s immunophenotype were performed to gain some additional insights in the potential causes of this rare phenomenon.

Injury of the circumflex artery is an uncommon but dangerous complication during mitral valve surgery. We report the case of a patient who presented an occlusion of the circumflex artery after a minimally invasive mitral valve repair, which was treated with angioplasty in the immediate post-operative period. (Level of Difficulty: Intermediate.)

The Sambucus canadensis species is used in traditional medicine mainly in indigenous communities as an anti-inflammatory, antiviral, to treat cough, fever and other ailments, however, its use must be validated on scientific bases. The aim of this study was to evaluate the genotoxic and cytotoxic effect of the ethanol extract of Sambucus canadensis in meristem cells of Allium sativum with 5 treatments at concentrations of 125, 250, 500, 1000 and 1500 mg/L. Two thousand cells were counted per treatment; the mitotic index (MI) and nuclear abnormalities (NA) were evaluated. Data were analyzed using variance analysis (ANOVA) and Chi square (X2) (p < 0.05). Root growth was found to be inhibited based on the concentration with statistically significant differences (p < 0.05). As the dose and exposure time of the ethanol extract increased, the MI decreased. The NA increased at the highest concentrations of 500, 1000 and 1500 mg/L and these differences were statistically significant compared to the control (p = 0.000). With the results obtained, it can be shown that the species has antiproliferative effects and genotoxic activity on the Allium sativum cell cycle, which can be extrapolated to other types of eukaryotic cells. Therefore, despite being a plant with health benefits, moderate use and low concentrations are recommended to avoid harmful effects.

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a heterogeneous group of clinical entities characterized by the common clinical evidence of myocardial infarction (MI) with non-obstructive coronary arteries on coronary angiography and without an overt cause for the MI. Platelets play a cornerstone role in the pathophysiology of MI with obstructive coronary arteries. Accordingly, antiplatelet therapy is recommended for treating patients with MI and obstructive coronary disease. However, the role of platelets in the pathophysiology of MINOCA patients is not fully defined, questioning the role of antiplatelet therapy in this setting. In this review, we will assess the role of antiplatelet therapy in MINOCA with a focus on the pathophysiology, therapeutic targets, current evidence, and future directions according to its different etiologies.

BackgroundThe long-term cardiovascular (CV) outcomes of COVID-19 have not been fully explored.MethodsThis was an international, multicenter, retrospective cohort study conducted between February and December 2020. Consecutive patients ≥18 years who underwent a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV2 were included. Patients were classified into two cohorts depending on the nasopharyngeal swab result and clinical status: confirmed COVID-19 (positive RT-PCR) and control (without suggestive symptoms and negative RT-PCR). Data were obtained from electronic records, and clinical follow-up was performed at 1-year. The primary outcome was CV death at 1-year. Secondary outcomes included arterial thrombotic events (ATE), venous thromboembolism (VTE), and serious cardiac arrhythmias. An independent clinical event committee adjudicated events. A Cox proportional hazards model adjusted for all baseline characteristics was used for comparing outcomes between groups. A prespecified landmark analysis was performed to assess events during the post-acute phase (31-365 days).ResultsA total of 4,427 patients were included: 3,578 (80.8%) in the COVID-19 and 849 (19.2%) control cohorts. At one year, there were no significant differences in the primary endpoint of CV death between the COVID-19 and control cohorts (1.4% vs. 0.8%; HRadj 1.28 [0.56-2.91]; p = 0.555), but there was a higher risk of all-cause death (17.8% vs. 4.0%; HRadj 2.82 [1.99-4.0]; p = 0.001). COVID-19 cohort had higher rates of ATE (2.5% vs. 0.8%, HRadj 2.26 [1.02-4.99]; p = 0.044), VTE (3.7% vs. 0.4%, HRadj 9.33 [2.93-29.70]; p = 0.001), and serious cardiac arrhythmias (2.5% vs. 0.6%, HRadj 3.37 [1.35-8.46]; p = 0.010). During the post-acute phase, there were no significant differences in CV death (0.6% vs. 0.7%; HRadj 0.67 [0.25-1.80]; p = 0.425), but there was a higher risk of deep vein thrombosis (0.6% vs. 0.0%; p = 0.028). Re-hospitalization rate was lower in the COVID-19 cohort compared to the control cohort (13.9% vs. 20.6%; p = 0.001).ConclusionsAt 1-year, patients with COVID-19 experienced an increased risk of all-cause death and adverse CV events, including ATE, VTE, and serious cardiac arrhythmias, but not CV death.Study registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT04359927.

Background Early generation drug‐eluting stents (DESs) showed a high grade of coronary endothelial dysfunction that was attributed to lack of stent reendothelialization. Endothelium‐dependent vasomotor response of current DESs and bioresorbable scaffolds (BRSs) remains unknown. This study sought to assess the device‐related endothelial function of current devices and to correlate neointima healing with endothelial function. Methods and Results A total of 206 patients from 4 randomized trials treated with the durable‐polymer everolimus‐eluting Xience (n=44), bioresorbable‐polymer sirolimus‐eluting Orsiro (n=35), polymer‐free biolimus‐eluting Biofreedom (n=24), bioactive endothelial‐progenitor cell‐capturing sirolimus‐eluting Combo DES (n=25), polymer‐based everolimus‐eluting Absorb (n=44), and Mg‐based sirolimus‐eluting Magmaris BRS (n=34) underwent endothelium‐dependent vasomotor tests and optical coherence tomography imaging, as per protocol, at follow‐up. Crude vasomotor responses of distal segments to low‐dose acetylcholine (10−6 mol/L) were different between groups: bioresorbablepolymer DEShad the worst (−8.4%±12.6%) and durable‐polymer DES had the most physiologic (−0.4%±11.8%; P=0.014). High‐dose acetylcholine (10−4 mol/L) showed similar responses between groups (ranging from −10.8%±11.6% to −18.1%±15.4%; P=0.229). Device healing was different between devices. Uncovered struts ranged from 6.3%±7.1% (bioresorbable‐polymer DES) to 2.5%±4.5% (bioactive DES; P=0.056). In multivariate models, endothelium‐dependent vasomotor response was associated with age, bioresorbable‐polymer DES, and angiographic lumen loss, but not with strut coverage nor plaque type. Endothelial dysfunction (defined as ≥4% vasoconstriction) was observed in 46.6% of patients with low‐dose and 68.9% with high‐dose acetylcholine, without differences between groups. Conclusions At follow‐up, endothelial dysfunction was frequently observed in distal segments treated with current stents without remarkable differences between devices. Although neointima healing was different between devices, poor healing was not associated with endothelial dysfunction.

Abstract Aims In May 2016, a new version of the European Society of Cardiology (ESC) Guidelines for the management of heart failure (HF) was released. The aim of this study was to describe the management of HF with reduced ejection fraction after the publication of ESC Guidelines. Methods and results The Linx registry is a multicentre, observational, cross‐sectional study from 14 Catalan hospitals that enrolled 1056 patients with HF and reduced left ventricular ejection fraction (≤40%) from 1 February to 30 April 2017 in outpatient cardiology clinics. Results were compared between hospitals according to their level of complexity in our own registry and compared with previously published registries similar to ours. Sacubitril/valsartan was prescribed to 23.9% of patients in our population, as a consequence, use of angiotensin‐converting enzyme inhibitor and angiotensin receptor blockers in monotherapy decreased to 48.1% and 16.9%, respectively, and prescription of beta‐blockers (91.8%), mineralocorticoid receptor antagonists (72.7%), and ivabradine (21.4%) remained similar to previous registries. Target doses of beta‐blockers (25.4%), angiotensin‐converting enzyme inhibitors (24.9%), angiotensin receptor blockers (7.7%), sacubitril/valsartan (8.1%), and mineralocorticoid receptor antagonists (19.7%) were accomplished in a low proportion of patients. Our results also suggest that prescription and up‐titration of class I HF drugs were greater in hospitals with higher level of complexity. Conclusions The Linx registry shows an appropriate adherence to pharmacological recommendations from ESC HF Guidelines despite a low proportion of patients reached target doses. Almost one‐quarter of patients were under treatment with sacubitril/valsartan a few months after ESC HF Guidelines recommendations.

Abstract Purpose The purpose of the study was to compare the safety and efficacy of autologous mesenchymal stem cells (MSCs) embedded in a xenogenic scaffold for repairing the supraspinatus tendon. Methods This was a randomized, double-blind and placebo-controlled trial evaluating patients with full-thickness rotator cuff tears (Eudra-CT, 2007–007630-19). Effectiveness was evaluated using the Constant score and a visual analogue pain scale (VAS). Constant score has four domains including pain (15 possible points), activities of daily living (20 possible points), mobility (40 possible points), and strength (25 possible points). Scores range from 0 points (most disability) to 100 points (least disability). The structural integrity of the repaired tendon was assessed by magnetic resonance imaging (MRI) according to Patte and Thomazeau classification criteria. The primary study end point was an improvement in the Constant score by 20 points at one year compared to initial assessment. Results The trial was stopped due to adverse effects observed in both groups. Only thirteen patients were included and analyzed. The Constant questionnaire showed a significant improvement in the MSC treatment group compared with the preoperative data (p = 0.0073). Secondary outcome measures were similar in both groups. Conclusions Our study showed preliminary inconclusive clinical outcomes in the patients treated with MSCs. Adverse events revealed the need for further approaches using scaffolds of a different nature or perhaps no scaffolds, in the context of small joints. Trial registration Eudra-CT, 2007-007630-19. Registered on 30 January 2008. Level of evidence A Level 1 of evidence treatment study.

RESUMEN Introducción y objetivos: La escala de puntuación PSP (pre-dilation, sizing and post-dilation), derivada del registro GHOST-EU, evalúa la relación entre la técnica de implante de los armazones bioabsorbibles y los resultados clínicos. El objetivo fue realizar una validación externa de la escala PSP y determinar su efecto en eventos adversos cardiacos en diversos escenarios clínicos y anatómicos. Métodos: Para la validación externa se emplearon los datos del registro REPARA (2.230 pacientes), mientras que se utilizó una base de datos común que combina datos de REPARA y GHOST-EU (3.250 pacientes) para evaluar el efecto de la técnica PSP en varios escenarios clínicos y anatómicos. Se usó PSP-1 y PSP-3 para calificar la calidad de la predilatación, el dimensionamiento de los armazones y la posdilatación. El objetivo primario fue la variable compuesta orientada al dispositivo (muerte cardiaca, infarto de miocardio del vaso diana y revascularización de la lesión diana) a 1 año. También se evaluó la trombosis definitiva o probable del armazón según los criterios del Academic Research Consortium. Resultados: Se trató a 303 (18,2%) pacientes con una PSP-1 óptima y a 182 (8,2%) con una PSP-3 óptima. La validación externa mostró que la escala PSP tiene un valor predictivo negativo muy alto para el objetivo primario compuesto orientado al dispositivo y la trombosis del armazón (91,8 y 89,1% para PSP-1; 98,4 y 97,3% para PSP-3, respectivamente). En pacientes con PSP-3 óptimo, el objetivo primario compuesto orientado al dispositivo y la trombosis del armazón fueron numéricamente inferiores en comparación con los pacientes sin PSP-3 óptimo (0,5 frente a 2,9%; p = 0,085; y 0,5 frente a 1,8%; p = 0,248, respectivamente). En la base de datos combinada, los beneficios de la escala PSP se observaron en diversos escenarios, excepto en el de infarto de miocardio con elevación del segmento ST, en el que se observó una tendencia hacia laausencia de beneficios de una técnica de PSP óptima (pinteracción = 0,100). Conclusiones: Una técnica de PSP óptima no se asoció con una tasa más baja del objetivo primario compuesto orientado al dispositivo. Se necesitan nuevos estudios para evaluar el impacto de la técnica de PSP con un seguimiento más prolongado.

ABSTRACT Introduction and objectives: The PSP (pre-dilation, sizing and post-dilation) score, derived from the GHOST-EU registry, has evaluated the relationship between the implantation technique of bioresorbable scaffolds and the clinical outcomes. The objective was to perform an external validation of the PSP technique and to determine its effect on adverse cardiac events in various clinical and anatomical scenarios. Methods: Data from the REPARA registry (2230 patients) were used for external validation, whereas a common database combining REPARA and GHOST-EU (3250 patients) data was used to evaluate the effect of PSP technique in various clinical and anatomical scenarios. PSP-1 and PSP-3 were used to score the appropriateness of pre-dilation, scaffold sizing, and post-dilation. The primary endpoint was 1-year device-oriented composite endpoint of cardiac death, target-vessel myocardial infarction, and target-lesion revascularization. The definite/probable scaffold thrombosis according to the Academic Research Consortium criteria was also evaluated. Results: A total of 303 (18.2%) patients were treated with an optimal PSP-1, and 182 (8.2%) with an optimal PSP-3. The external validation showed that PSP has a very high negative predictive value for device-oriented composite endpoint and scaffold thrombosis (91.8% and 89.1% for PSP-1; 98.4% and 97.3% for PSP-3, respectively). Patients with an optimal PSP-3 had a numerically lower rate of device-oriented composite endpoint and scaffold thrombosis compared to those without it (0.5% vs 2.9%; P = .085 and 0.5% vs 1.8%; P = .248, respectively). In the merged database, PSP benefits were seen on many scenarios, except in the ST-segment elevation myocardial infarction where a trend towards no benefit of an optimal PSP technique was present (Pinteraction = .100). Conclusions: In the REPARA registry, at 1-year follow-up, an optimal PSP technique was not associated with a lower rate of device-oriented composite endpoint. Further research is necessary to assess the impact of the PSP technique in longer follow-ups.

In patients with acute and chronic coronary artery disease undergoing percutaneous coronary intervention (PCI), dual antiplatelet therapy (DAPT) has been the cornerstone of pharmacotherapy for the past two decades. Although its antithrombotic benefit is well established, DAPT is associated with an increased risk of bleeding, which is independently associated with poor prognosis. The improvement of the safety profiles of drug-eluting stents has been critical in investigating and implementing shorter DAPT regimens. The introduction into clinical practice of newer generation oral P2Y12 inhibitors such as prasugrel and ticagrelor, which provide more potent and predictable platelet inhibition, has questioned the paradigm of standard DAPT durations after coronary stenting. Over the last five years, several trials have assessed the safety and efficacy of P2Y12 inhibitor monotherapy after a short course of DAPT in patients treated with PCI. Moreover, ongoing studies are testing the role of P2Y12 inhibitor monotherapy immediately after PCI in selected patients. In this review, we provide up-to-date evidence on the efficacy and safety of P2Y12 inhibitor monotherapy after a short period of DAPT compared to DAPT in patients undergoing PCI as well as outcomes associated with P2Y12 inhibitor monotherapy compared to aspirin for long-term prevention.

Breve nota acerca del profesor de química de la PUCP Miguel Ángel Chong Cáceres, fallecido a inicios de 2021

MicroRNAs (miRNA) are major regulators of intercellular communication and key players in the pathophysiology of cardiovascular disease. This study aimed to determine the miRNA fingerprint in a cohort of 53 patients with acute myocardial infarction (AMI) with non-ST-segment elevation (NSTEMI) relative to miRNA expression in healthy controls (n = 51). miRNA expression was initially profiled by miRNA array in the serum of patients undergoing cardiac catheterization during NSTEMI (n = 8) and 1 year past the event (follow-up, n = 8) and validated in the entire cohort. In total, 58 miRNAs were differentially expressed during AMI (p < 0.05), while 36 were modified at follow-up (Fisher’s exact test: p = 0.0138). Enrichment analyses revealed differential regulation of biological processes by miRNA at each specific time point (AMI vs. follow-up). During AMI, the miRNA profile was associated mainly with processes involved in vascular development. However, 1 year after AMI, changes in miRNA expression were partially related to the regulation of cardiac tissue morphogenesis. Linear correlation analysis of miRNA with serum levels of cytokines and chemokines revealed that let-7g-5p, let-7e-5p, and miR-26a-5p expression was inversely associated with serum levels of pro-inflammatory cytokines TNF-α, and the chemokines MCP-3 and MDC. Transient transfection of human endothelial cells (HUVEC) with let-7e-5p inhibitor or mimic demonstrated a key role for this miRNA in endothelial function regulation in terms of cell adhesion and angiogenesis capacity. HUVEC transfected with let-7e-5p mimic showed a 20% increase in adhesion capacity, whereas transfection with let-7e-5p inhibitor increased the number of tube-like structures. This study pinpoints circulating miRNA expression fingerprint in NSTEMI patients, specific to the acute event and changes at 1-year follow-up. Additionally, given its involvement in modulating endothelial cell function and vascularization, altered let-7e-5p expression may constitute a therapeutic biomarker and target for ischemic heart disease.

We have evaluated cardiac function and fibrosis in infarcted male Wistar rats treated with MitoQ (50 mg/kg/day) or vehicle for 4 weeks. A cohort of patients admitted with a first episode of acute MI were also analyzed with cardiac magnetic resonance and T1 mapping during admission and at a 12-month follow-up. Infarcted animals presented cardiac hypertrophy and a reduction in the left ventricular ejection fraction (LVEF) and E- and A-waves (E/A) ratio when compared to controls. Myocardial infarction (MI) rats also showed cardiac fibrosis and endoplasmic reticulum (ER) stress activation. Binding immunoglobulin protein (BiP) levels, a marker of ER stress, were correlated with collagen I levels. MitoQ reduced oxidative stress and prevented all these changes without affecting the infarct size. The LVEF and E/A ratio in patients with MI were 57.6 ± 7.9% and 0.96 ± 0.34, respectively. No major changes in cardiac function, extracellular volume fraction (ECV), or LV mass were observed at follow-up. Interestingly, the myeloperoxidase (MPO) levels were associated with the ECV in basal conditions. BiP staining and collagen content were also higher in cardiac samples from autopsies of patients who had suffered an MI than in those who had died from other causes. These results show the interactions between mitochondrial oxidative stress and ER stress, which can result in the development of diffuse fibrosis in the context of MI.

Abstract Coronavirus disease 2019 (COVID‐19) is an infectious disease caused by severe acute respiratory syndrome coronavirus‐2, which has posed a significant threat to global health. Although the infection is frequently asymptomatic or associated with mild symptoms, in a small proportion of patients it can produce an intense inflammatory and prothrombotic state that can lead to acute respiratory distress syndrome, multiple organ failure, and death. Angiotensin‐converting enzyme 2, highly expressed in the respiratory system, has been identified as a functional receptor for severe acute respiratory syndrome coronavirus‐2. Notably, angiotensin‐converting enzyme 2 is also expressed in the cardiovascular system, and there are multiple cardiovascular implications of COVID‐19. Cardiovascular risk factors and cardiovascular disease have been associated with severe manifestations and poor prognosis in patients with COVID‐19. More important, patients with COVID‐19 may have thrombotic and coagulation abnormalities, promoting a hypercoagulable state and resulting in an increased rate of thrombotic and thromboembolic events. This review will describe the pathophysiological characteristics of the cardiovascular involvement following infection by severe acute respiratory syndrome coronavirus‐2, with a focus on thrombotic and thromboembolic manifestations and implications for antithrombotic management.

BackgroundPatients presenting with the coronavirus-2019 disease (COVID-19) may have a high risk of cardiovascular adverse events, including death from cardiovascular causes. The long-term cardiovascular outcomes of these patients are entirely unknown. We aim to perform a registry of patients who have undergone a diagnostic nasopharyngeal swab for SARS-CoV-2 and to determine their long-term cardiovascular outcomes.Study and designThis is a multicenter, observational, retrospective registry to be conducted at 17 centers in Spain and Italy (ClinicalTrials.gov number: NCT04359927). Consecutive patients older than 18 years, who underwent a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV2 in the participating institutions, will be included since March 2020, to August 2020. Patients will be classified into two groups, according to the results of the RT-PCR: COVID-19 positive or negative. The primary outcome will be cardiovascular mortality at 1 year. The secondary outcomes will be acute myocardial infarction, stroke, heart failure hospitalization, pulmonary embolism, and serious cardiac arrhythmias, at 1 year. Outcomes will be compared between the two groups. Events will be adjudicated by an independent clinical event committee.ConclusionThe results of this registry will contribute to a better understanding of the long-term cardiovascular implications of the COVID19.

En esta pequeña nota se recuerdan las características fuera de lo comunes del autor de uno de los libros más conocidos en el área de la Química inorgánica: James E. Huheey. Este químico estadounidense fue un apasionado de la herpetología, donde llego a ser tan conocido entre sus pares como en el área de química.

Various studies have been done on shifting toward technology-based second language (L2) education. However, the influence of psycho-emotional factors on students' technology acceptance is overlooked. To fill this gap, the present quantitative study examined the role of students' achievement emotions and technological self-efficacy in predicting their technology acceptance in China. To this end, 380 Chinese students were invited to complete three questionnaires. The results of structural equation modeling revealed that Chinese L2 students' achievement emotions and technological self-efficacy are significant predictors of their technology acceptance; technological self-efficacy uniquely could explain 59% of its variance and students' achievement emotions could explain 75% of its variance. The study also draws some conclusions and offers implications for L2 teachers, students, and school managers to foster the acceptance of technology in L2 education.

Adolescent school connectedness generally protects from risk behaviors such as tobacco use; however, its relationship to e-cigarette use is unclear. This study examines the relationship between adolescent school connectedness and e-cigarette susceptibility in a diverse longitudinal sample. This secondary analysis of a school-based intervention surveyed 608 middle (66%) and high school (34%) students from 10 schools at 3 time points over 1 year. At baseline, respondents had a mean age of 14 years, 54% were female, and 71% were BIPOC (Black, Indigenous, People of Color). Logistic regression models examined unadjusted and adjusted associations between school connectedness (both baseline and concurrent) and e-cigarette susceptibility over time. E-cigarettes represented the most prevalent form of current nicotine-containing product use in spring 2019 (2.3%), and most respondents reported no e-cigarette susceptibility (69%). E-cigarette susceptibility remained relatively stable during the study. Higher baseline school connectedness levels were associated with lower odds of e-cigarette susceptibility over time. Similarly, higher concurrent school connectedness scores were associated with lower odds of e-cigarette susceptibility over time: spring 2019 (OR, 0.39; 95% CI, 0.32, 0.47), fall 2019 (OR, 0.49; 95% CI, 0.34, 0.72), and spring 2020 (OR, 0.64; 95% CI, 0.47, 0.87). Findings were similar for middle and high school students and did not differ significantly after adjusting for other covariates. Adolescents' school connectedness appears to protect from e-cigarette susceptibility over time, underscoring the importance of promoting positive school experiences to reduce adolescent risk e-cigarette use.

Introduction: Neuroendocrine tumors (NETs) occur more often in lungs, gastrointestinal tract, or pancreas. Data about terminology and grading of NETs in rare locations are scarce and variable, and they have been reported mainly as case reports. Materials and Methods: We here describe our experience with NETs in unusual locations. We have reviewed all NETs diagnosed in our institution and summarized their clinicopathological features. We have also reviewed the literature and discussed the main characteristics of NETs in each site. Results: Two hundred and forty-three primary NETs were diagnosed. About 55.2% of patients were men and the mean age was 62 years. About 90.7% of NETs were located in lungs, gastrointestinal tract, or pancreas, and 50.8% of them were low-grade tumors. We identified 13 NETs in rare locations: breast, ovary, endometrium, vulva, uterine cervix, extrahepatic biliary tract, kidney, sinonasal tract, and thymus. Three additional tumors were diagnosed by the senior author in other institution. Patients were asymptomatic or presented with nonspecific symptoms. All NETs were treated with surgery and 31% of patients received adjuvant therapy. There were 10 Grade 3 (62.5%), 2 Grade 2 (12.5%), and 4 Grade 1 (25%) tumors. Mean follow-up was 72 months. About 60% of G3 tumors recurred or progressed. G2 tumors were located in breast, and both patients are stable. About 50% of G1 tumors recurred or progressed (both renal NETs). Conclusions: NETs in rare locations are heterogeneous, and their behavior does not seem to correlate absolutely with tumor grade. More studies are needed to clarify the role of proliferation rate in these tumors.

The concurrent management of type 2 diabetes mellitus and heart failure presents several challenges and unmet clinical needs. The sodium-glucose cotransporter 2 inhibitors (SGLT2i) are new generation of oral hypoglycemic agents, they inhibit renal glucose reabsorption and increase renal glucose excretion, thus lowering plasma glucose levels and contributing to a modest reduction in HbA1C. In two pivotal randomized clinical trial, SGLT2i have showed a clinically important reduction in cardiovascular mortality and hospitalization due to heart failure. However, also important adverse effects such as increased risk of bone fractures and lower limb amputations were found. Currently, physiological mechanisms leading to cardiovascular benefits with SGLT2i are not completely understood, but it seems accepted that some of these benefits are related to non-glycemic effects. In this review, we analyze the available clinical evidence focusing in cardiovascular outcomes and heart failure, physiological mechanism of action, and comment on future directions of research.

Climate variability imposes greater challenges on family farming and especially on rural communities in vulnerable mountainous regions such as the Andes in Latin America. Changes in rainfall patterns and fluctuations in temperatures cause a greater frequency of extreme events, increased pests, and crop diseases, which even lead to food insecurity in communities that depend on self-production for survival. This is why strategies need to be developed to face this new scenario. Two cases of adaptation experiences to the effects of climate variability in rural communities in Chile (Araucanía Region) and Colombia (Cauca Department) were analyzed on this paper. For this, a mixed methodological approach was adopted that included the analysis of climate data, socioeconomic, and productive characterization of the communities, and a characterization of adaptation practices for both cases. The results show various ways of adapting mainly to changes in the availability and access of water for the development of agriculture and for domestic use. Likewise, it is shown that in order to be successful, the measures for facing climate variability must be part of coordinated strategies under a community-based adaptation approach and not developed in isolation.

COVID-19 has shown significant morbidity with the involvement of multiple systems, including the cardiovascular system. Cardiovascular manifestations in the acute phase can include myocardial injury itself, myocardial infarction, venous thromboembolic events, myocarditis, Takotsubo syndrome, and different arrhythmic events. Myocardial injury defined by the rise of cardiac biomarkers in blood has been found in multiple studies with a prevalence of about 20%. Its presence is related to worse clinical outcomes and in-hospital mortality. The mechanisms of myocardial injury have been the subject of intense research but still need to be clarified. The characterization of the cardiac affectation with echocardiography and cardiac magnetic resonance has found mixed results in different studies, with a striking incidence of imaging criteria for myocarditis. Regarding post-acute and chronic follow-up results, the persistence of symptoms and imaging changes in recovered COVID-19 patients has raised concerns about the duration and the possible significance of these findings. Even though the knowledge about this disease has increased incredibly in the last year, many aspects are still unclear and warrant further research.

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level. Through specific base pairing with their targets messenger RNAs (mRNA), miRNA can modify cell phenotype and function. Several miRNAs are aberrantly expressed in diseased arteries and may influence different features of vascular remodeling, including neointimal formation and diminished re-endothelialization. This review will discuss the clinical implications of miRNAs in the field of vascular remodeling and their potential role as diagnostic and therapeutic tools. miRNA modulation offers a promising strategy for therapeutic intervention to inhibit smooth muscle cell proliferation and enhance endothelial regeneration after percutaneous coronary intervention (PCI) in order to reduce restenosis and late thrombosis.

Background. Nutritional deficiencies may aggravate the course of chronic hepatitis C (CHC). Our aim has been to perform a comprehensive analysis of body composition and nutritional deficiencies in CHC patients in non-cirrhotic and compensated cirrhotic stages to correlate the detected deficiencies with the fibrosis stage.Material and methods. Body multifrequency bioimpedance analysis (BIA) and a wide and simultaneous analytical profile were prospectively performed in 74 CHC patients (36 male) with known METAVIR fibrosis stage established with liver biopsy or transient elastography. Results were analyzed to identify deviations from the normal range and variations according to the fibrosis stage.Results. Body fat compartment was greater in women. Body composition did not change among the 4 stages of liver fibrosis. Low levels (< 30 μg/L) of vitamin D were detected in 74.3% of patients irrespective of the fibrosis stage. Most analytical results remained into the normal range with the exceptions of thrombocytopenia and vitamin A deficiency, that were limited to the stage 4 of fibrosis, and low Zn and LDL-cholesterol values, that were frequently found in patients with advanced (F3 and F4) fibrosis stage.Conclusion. Body composition and most biochemical parameters, including cyanocobalamin, folic acid and vitamin E, are well preserved in compensated patients with CHC, with the exception of generalized vitamin D insufficiency and of deficiencies of vitamin A and zinc that are restricted to the more advanced, although still compensated, stages of the disease.

This academic article tries to analyze the form how the Law 790 of 2002 by which the program of renovation of the public administration with the restriction of the "social detent" settled down, in his article 12 it generated a discrimination for the parents head of household, to those who it was not sheltered to them with the propose exceptions, leaving without sustenance to the children of these families and the arguments that the Constitutional Court used to declare conditionally exequible east article and to preserve the rights of these children through the labor stability of its parents.