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Resumen Introduccion La deteccion precoz del cancer de cervix requiere la implementacion de programas de cribado del virus del papiloma humano (VPH). Sin embargo, existen discrepancias en la optimizacion de esas estrategias. Se evalua el rendimiento de 10 protocolos basados en tecnicas moleculares, citologicas o combinadas en cribado primario. Material y metodos Se disena un estudio ciego, prospectivo e intervencionista en 1.977 mujeres de 35 anos. La determinacion molecular se realizo por la plataforma Cobas 4800 HPV. Los analisis citologicos se realizaron en las mismas muestras sin conocimiento del resultado molecular. Todas las mujeres en las que se detectaba VPH-16/VPH-18 o presentaban alteracion citologica y deteccion de otros genotipos de alto riesgo (VPHar) eran derivadas a colposcopia. Resultados El ensayo molecular detecto presencia de VPHar en el 12,5% de las mujeres, mientras solo el 8,1% de las citologias fueron patologicas. El 19,5% de las pacientes derivadas a colposcopia revelaron lesiones de alto grado, estando VPH-16 presente en el 65,3% de ellas. En 6 de esas ocasiones (VPH-16 siempre presente) la citologia habia sido informada como normal. El seguimiento al ano de las mujeres con citologia normal y deteccion de VPHar identifico una lesion HSIL/CIN2+ (asociada a VPH-33). En el estudio comparativo con otras estrategias el protocolo denominado CRYGEN 16/18 rindio el mejor equilibrio de sensibilidad y especificidad con la menor derivacion a colposcopia. Conclusiones La realizacion de deteccion molecular de VPH con genotipado parcial en primera linea, al menos VPH-16, con derivacion directa a colposcopia, aumenta la tasa de deteccion de lesiones HSIL/CIN2+.

The aim of this substudy of the EXAMINATION-EXTEND was to analyze 10-year outcomes according to the patient's age at the time of the first ST-elevation myocardial infarction (STEMI). Of 1,498 patients with STEMI included in the EXAMINATION-EXTEND study, those with a previous history of coronary ischemic even or ischemic stroke were excluded from this analysis. The remaining 1,375 patients were divided into 4 age groups: 75 years. The primary end point was 10-year patient-oriented composite end point (POCE) of all-cause death, any MI, or any revascularization. At 10-year follow-up, patients aged 75 years, led by a lower incidence of all-cause death (75 years: 61.6%, p = 0.001). Cardiac death was more prevalent in the older group (75 years: 35.5%, p = 0.001). In the landmark analyses, between 5- and 10-year follow-up, young patients exhibited a higher incidence of any revascularization (65 years: 1.6%, p = 0.001). In conclusion, in patients with a first STEMI, advanced age was associated with high rates of POCE at 10-year follow-up due to all-cause and cardiac death. Conversely, younger patients exhibited a high risk of revascularization at long-term follow-up.

Background Phase II randomized controlled trials (RCTs) on factor(F)XI inhibitors have shown promising results but they were burdened by low statistical power for clinical outcomes. Methods We performed a systematic review and meta-analysis of RCT comparing FXI inhibitors versus other anticoagulants (enoxaparin or direct oral anticoagulants, DOACs) or versus placebo on top of antiplatelet therapy. Results Eight RCTs testing FXI inhibitors (ISIS 416858, osocimab, abelacimab, milvexian, asundexian) and enrolling 9,216 patients were included. Compared with enoxaparin, FXI inhibitors were associated with reduced any-bleeding (risk ratio [RR]: 0.49, 95% confidence interval [CI]: 0.31–0.77), no difference in major bleeding (RR: 0.96, 95% CI: 0.41–2.28), and reduced trial-defined efficacy endpoint (RR: 0.62, 95% CI: 0.49–0.79), the latter driven by the high-dose regimens. Compared with DOACs, FXI inhibitors were associated with a trend toward reduced any-bleeding (RR: 0.66, 95% CI: 0.31–1.38) and no difference in major bleeding (RR: 1.03, 95% CI: 0.22–4.78) or in trial-defined efficacy endpoint (RR: 1.23, 95% CI: 0.88–1.70). Compared with placebo, FXI inhibitors were associated with increased any-bleeding (RR: 1.25, 95% CI: 1.08–1.43) and a trend toward increased major bleeding (RR: 1.21, 95% CI: 0.75–1.93), both driven by high-dose regimens, with no difference in trial-defined efficacy endpoint (RR: 1.02, 95% CI: 0.92–1.13). Conclusion Results of this meta-analysis on FXI inhibitors suggest increased safety and efficacy compared with enoxaparin and modest increased safety compared with DOACs. The use of FXI inhibitors in adjunct to antiplatelet therapy versus placebo appears to be associated with a dose-dependent increase in bleeding without any difference in efficacy. Study registration This study is registered in PROSPERO (CRD42022367706).

Citations in a scientific paper reference other studies and form the information backbone of that paper. If cited literature is valid and non-retracted, an analysis of citations can offer unique perspectives about the supportive or contradictory nature of a statement. Yet, such analyses are still limited by the relative lack of access to open citation data. The creation of open citation databases (OCDs) allows for data analysts, bibliometric specialists, and other academics interested in such topics to independently verify the validity and accuracy of a citation. Since the strength of an individual’s curriculum vitae can be based on, and assessed by, metrics (citation counts, altmetric mentions, journal ranks, etc.), there is interest in appreciating citation networks and their link to research performance. Open citations would thus not only benefit career, funding, and employment initiatives, but they could also be used to reveal citation rings, abusive author–author or journal–journal citation strategies, or to detect false or erroneous citations. OCDs should be open to the public, and publishers have a moral responsibility of releasing citation data for free use and academic exploration. Some challenges remain, including long-term funding, and data and information security.

The persistence of elevated rates of ischemic recurrences despite the use of antiplatelet therapy among patients with atherosclerotic disease together with the understanding of the pivotal role of coagulation in the thrombo-inflammatory processes involved in the pathogenesis of atherosclerosis and its complications has fostered the development of treatments targeting both platelets and coagulation, a strategy known as dual-pathway inhibition (DPI).In this review we discuss the recent advancements in the understanding of the interplay between coagulation, platelets and inflammation involved in the pathophysiology of atherosclerosis and atherothrombosis, as the rationale for the implementation of a DPI strategy. We also discuss the available pharmacodynamic (PD) evidence and clinical implications with the use of DPI in patients with atherosclerotic disease.The implementation of a DPI by adding the so-called "vascular dose of rivaroxaban" (i.e., 2.5 mg bis in die), on top of antiplatelet therapy has consistently been associated with reduced levels of thrombin generation in PD studies and with reduced ischemic event rates at the cost of increased bleeding compared to antiplatelet therapy alone. Further research is warranted to best define patients in whom a DPI regimen has the best safety and efficacy profile.

INTRODUCTION AND OBJECTIVES: The DECADE cooperation is a pooled analysis of individual patient data from drug-eluting stent (DES) trials with a 10-year follow-up. This analysis reports the risk of definite stent thrombosis (ST) through to 10 years after percutaneous coronary intervention (PCI) in patients treated with early- and new-generation DES.METHODS: Individual patient data from 5 DES trials with a 10-year follow-up were pooled. The primary endpoint was definite ST up to 10 years after PCI. Patients were divided into 2 groups as per the generation of DES implanted (early and new DES). Individual participant data were analyzed using a 1-stage approach.RESULTS: We included 9700 patients, 6866 in the new DES group and 2834 in the early DES group. Through to 10 years, definite ST occurred in 69 of 6866 patients treated with new DES and in 91 of 2834 patients treated with early DES (1.0% vs 3.5%, adjusted hazard ratio, 0.32; 95%CI, 0.23-0.45). The rate of definite ST was lower in the new DES group than in the early DES group from 1 to 5 years (rate ratio, 0.14; 95%CI, 0.08-0.26) and from 5 to 10 years (rate ratio, 0.23; 95%CI, 0.08-0.61) after PCI.CONCLUSIONS: The incidence of definite ST through to 10 years after PCI with new-generation DES was 1%. New-generation DES are associated with a lower 10-year incidence of definite ST than early-generation DES, particularly beyond 1 year after PCI.

INTRODUCTION AND OBJECTIVES The DECADE cooperation is a pooled analysis of individual patient data from drug-eluting stent (DES) trials with a 10-year follow-up. This analysis reports the risk of definite stent thrombosis (ST) through to 10 years after percutaneous coronary intervention (PCI) in patients treated with early- and new-generation DES. METHODS Individual patient data from 5 DES trials with a 10-year follow-up were pooled. The primary endpoint was definite ST up to 10 years after PCI. Patients were divided into 2 groups as per the generation of DES implanted (early and new DES). Individual participant data were analyzed using a 1-stage approach. RESULTS We included 9700 patients, 6866 in the new DES group and 2834 in the early DES group. Through to 10 years, definite ST occurred in 69 of 6866 patients treated with new DES and in 91 of 2834 patients treated with early DES (1.0% vs 3.5%, adjusted hazard ratio, 0.32; 95%CI, 0.23-0.45). The rate of definite ST was lower in the new DES group than in the early DES group from 1 to 5 years (rate ratio, 0.14; 95%CI, 0.08-0.26) and from 5 to 10 years (rate ratio, 0.23; 95%CI, 0.08-0.61) after PCI. CONCLUSIONS The incidence of definite ST through to 10 years after PCI with new-generation DES was 1%. New-generation DES are associated with a lower 10-year incidence of definite ST than early-generation DES, particularly beyond 1 year after PCI.

The long-term safety and performance of magnesium-based bioresorbable scaffolds (MgBRS) in ST-segment-elevation myocardial infarction (STEMI) patients are uncertain.The aim of this study was to report the 3-year clinical outcomes of the MAGSTEMI trial.This investigator-driven, multicentre, randomised, single-blind, controlled trial randomised STEMI patients 1:1 to MgBRS or to permanent metallic sirolimus-eluting stents (SES) at 11 academic centres. The main secondary endpoints included device-oriented composite endpoints (DoCE) and patient-oriented composite endpoints (PoCE), their individual components, any bleeding, and device thrombosis rate. All endpoints were defined according to the Academic Research Consortium. Events were adjudicated by an independent committee.Three-year clinical follow-up was obtained in 142 (90.0%) patients. At 3-year follow-up, MgBRS were associated with a higher rate of DoCE than SES (13 [17.6%] vs 5 [6.6%], diff -11.0 [95% CI: -21.3 to -0.7]; p=0.038). This difference was driven by an increased incidence of DoCE within the first year of follow-up. In the landmark analysis, there was no difference between 1 and 3 years (0 [0.0%] vs 1 [1.4%]; p=1.000). The difference in the rate of DoCE was driven by a higher incidence of target lesion revascularisation (TLR) in the MgBRS group compared to SES (12 [16.2%] vs 4 [5.3%]; diff -10.9% [95% CI: -20.7 to -1.2]; p=0.030). The difference in TLR was observed during the first year, with no further differences observed between 1 and 3 years (0 [0.0%] vs 1 [1.4%]; p=1.000).At 3-year follow-up, MgBRS were associated with a higher rate of TLR, which was clustered within the first year, compared to SES.

Precision medicine is a medical model that proposes the customization of medical treatments to the individual patient, as opposed to a one-drug-fits-all model. Such a “personalized medicine” approach has been widely adopted in several medical fields, such as cancer medicine, but the implementation of precision medicine in cardiovascular medicine has not been similarly straightforward. Because pharmacogenomics plays an important role in the safety and efficacy of cardiovascular drug therapy, there has been a great interest in the use of tools aiming at personalizing antiplatelet therapy. Moreover, antiplatelet therapy is essential for the treatment of cardiovascular patients to reduce the risk of thrombotic complications, particularly those undergoing percutaneous coronary intervention, but it is inevitably associated with increased bleeding risk. In this review, the authors discuss the rationale, summarize the evidence and discuss the current and future directions for the personalization of antiplatelet treatment regimens in patients undergoing percutaneous coronary intervention.

In the molecular era, the Laurén system is still a cost-effective and widely implemented classification for gastric cancer (GC) and it has been recently associated with clinical, histological and molecular features of these tumors. Despite recent advances in the understanding of the molecular biology of GC, there is a need to develop new prognostic tools for patient stratification in clinical practice. Thus, the identification of easily available prognostic factors in patients with intestinal and diffuse-type tumors can significantly improve risk assessment and patient stratification in GC.To identify clinicopathological differences, risk factors, and to develop cost-effective prognostic scores for patients with intestinal and diffuse-type GC.Retrospective study of all patients undergoing surgery for GC at a tertiary referral center from 2001 to 2019. 286 cases met inclusion criteria (intestinal: 190, diffuse: 96). Clinical data and gross findings were collected. All specimens were reviewed by two independent pathologists and a detailed protocol for histologic evaluation was followed. Five tissue microarrays (TMAs) were constructed and sections of the TMA block were immunostained for HERCEPTEST, MSH2, MSH6, MLH1 and PMS2. Statistical analyses were performed and prognostic scores were developed based on hazard ratios.Intestinal and diffuse-type GC showed different epidemiological, clinicopathological and prognostic features. Diffuse tumors were significantly associated with younger age, less symptomatology, flat morphology, deeper invasion, perineural infiltration, advanced stage at diagnosis, administration of adjuvant therapy and poorer prognosis. Intestinal lesions were fungoid or polypoid, showed necrosis, desmoplasia, microsatellite instability and HERCEPTEST positivity and were diagnosed at earlier stages. Tumor depth, desmoplasia, macroscopic type and lymph node involvement were independently related to the Laurén subtype. Furthermore, intestinal and diffuse GC were associated with different risk factors for progression and death. Vascular invasion, perineural infiltration and growth pattern were important prognostic factors in intestinal-type GC. On the contrary, tumor size and necrosis were significant prognosticators in diffuse-type GC. Our recurrence and cancer-specific death scores for patients with intestinal and diffuse-type GC showed an excellent patient stratification into three (diffuse GC) or four (intestinal) prognostic groups.Our findings support that Laurén subtypes represent different clinicopathological and biological entities. The development of specific prognostic scores is a useful and cost-effective strategy to improve risk assessment in GC.

En la última década, se ha podido ver un aumento de investigaciones con el fin de estudiar cómo implementar el feedback en la competencia escrita de los estudiantes de inglés como lengua extranjera en la Educación Superior; sin embargo, estos estudios en Educación Secundaria son escasos. El objetivo principal de este estudio, realizado en el tercer curso de Educación Secundaria Obligatoria, es investigar cómo el alumnado y el profesor supervisor perciben la retroalimentación antes de un ciclo de intervenciones de investigación-acción. Además, se pretende estudiar los efectos de la intervención en los alumnos en cuanto al feedback que reciben en la competencia escrita en inglés. Para ello, el estudio se llevó a cabo combinando instrumentos de investigación cuantitativos y cualitativos: dos cuestionarios de escala Likert, una entrevista semiestructurada y un portafolio de escritura. La estrategia de la alfabetización en el feedback, entendida como la diposición, la comprensión y el compromiso para aplicar la retroalimentación, se llevó a cabo en este estudio para potenciar la escritura de los estudiantes a través de talleres de retroalimentación o feedback. Los estudiantes participaron en actividades para discutir, decodificar y actuar sobre el feedback que recibieron después de presentar tres tareas de escritura. Los resultados sugieren que los estudiantes adquirieron estrategias para detectar y corregir sus propios errores, desarrollaron la fluidez de la escritura y llegaron a apreciar la utilidad de la retroalimentación para asumir un papel activo en su propio aprendizaje.

El Aprendizaje-Servicio (ApS) es una metodología que combina las experiencias de aprendizaje pragmáticas e inclusivas, al tiempo que se satisfacen las necesidades de la sociedad. Si a ello se le suma una práctica de actividad física (AF) controlada y juegos socializadores a través de la metodología de Respuesta Física Total (en inglés Total Physical Response, TPR), la adquisición de una lengua extranjera podría resultar más efectiva y natural. El objetivo principal de este estudio es el análisis de la adquisición de las competencias que el ApS produce en el alumnado universitario de la asignatura de la mención de inglés, Didáctica de la Literatura Infantil y Juvenil, en el Grado de Primaria de la Facultad de Ciencias de la Educación y del Deporte de Melilla de la Universidad de Granada. A partir de las experiencias de 14 estudiantes sobre la enseñanza del inglés como Lengua Extranjera (ILE) en un programa ApS con colectivo migrante a través de TPR se observa como estas metodologías suponen un espacio pedagógico nuevo para los docentes de inglés, y a su vez, la ruptura de una enseñanza tradicional. Del mismo modo, como resultado principal se puede constatar que el ApS aplicado al proceso de enseñanza y aprendizaje de la adquisición de una lengua extranjera, con la AF como instrumento, es una metodología que propicia el desarrollo de competencias académicas, profesionales y personales del alumnado universitario de la mención de Inglés del Grado de Educación Primaria. Abstract. Service-Learning (SL) is an educative methodology that combines student’s pragmatic and inclusive learning, and benefits community. In addition, together with supervised physical activity (PA) and Total Physical Response (TPR) group games, it could make the foreign language learning more natural and effective. The main aim of this study is to analyse the effects of SL competences on university students of Primary Education specialised in English language teaching. The participants were students of the Faculty of Education and Sport Sciences, Campus of Melilla, University of Granada, and the course was Didactics of Literature for Children and Young People in a Foreign Language: English. The SL experiences of 14 students who offered services to migrants by Teaching English as a Foreign Language (TEFL) with TPR as a main tool, showed to the students a new pedagogical space and a break in traditional teaching practices. In conclusion, TPR-based SL is a useful methodology to teach English and obtain new perspective of TEFL. Moreover, PA is a tool that favours the development of academic, professional, and personal skills of university students of Primary Education specialised in English language teaching.

El objetivo de la presente investigación fue realizar el diagnóstico de brucelosis de ganado bovino nativo del Norte de México con cultivo de muestras de leche, seroaglutinación con rosa de bengala y rivanol según la NOM-041-ZOO-1995. Se seleccionó una población de 1600 bovinos hembra adultos lecheros raza Holstein-Friesian de 38 a 48 meses de edad. Cada muestra estuvo compuesta de leche extraída proveniente de todos los cuarterones, tomándose ~10 mL de leche por cada pezón. Sembradas en TSA/5% SBE y 5% CO2 atm, 37°C/21 d, subcultivos en agar Brucella y agar TSI 37°C/21 d y pruebas bioquímicas para detectar la producción de H2S y ureasa, y así confirmar la identificación de Brucella. El suero obtenido fue para procesar rosa de bengala y rivanol. Resulto un total de 460 cultivos de leche positivo a Brucella spp, de las cuales 417 (90.65%) fueron positivas a rosa de bengala y 43 (9.35%) negativas. Al procesar rivanol, fueron 338 (73.48%) positivas y 122 (26.52%). Rivanol sigue siendo buen referente para diagnóstico de brucelosis por infección, ya que permite descartar tanto muestras positivas por cultivo positivo en leche como por el diagnostico en suero con rosa de bengala.

Background Coronary vascular function of a chronic coronary total occlusion (CTO) immediately after recanalization is known to be poor and to be partially improved by pre-treatment with loading dose of ticagrelor vs. clopidogrel . It is unknown if this vascular dysfunction is maintained at long-term follow-up and may be improved by 1-year dual antiplatelet therapy (DAPT). Methods The TIGER is a prospective, open-label, two parallel-group controlled clinical trial , which 1:1 randomized 50 CTO patients to pre-PCI loading dose and subsequent 1-year DAPT with ticagrelor vs. clopidogrel. Coronary blood flow (CBF) under stepwise adenosine infusion was assessed after drug loading dose and at follow-up and compared between the two drug groups, adjusting for time of follow-up. Results Out of 50 patients with index CBF evaluation, 38 (76%) patients underwent angiographic follow-up (23 and 15 at 1 and 3-year, respectively) and Doppler data was available in 35 (70%). A high CBF area under the curve (AUC), already observed after loading dose in ticagrelor vs. clopidogrel group (p = 0.027), was maintained at follow-up (AUC 34815.22 ± 24,206.06 vs. AUC 22712.47 ± 13,768.95; p = 0.071). Specifically, whereas high ticagrelor loading dose-related CBF was sustained at follow-up (p = 0.933), clopidogrel loading dose-related CBF increased at follow-up (p = 0.039). Conclusion The TIGER trial showed that DAPT with ticagrelor maintained a non-significantly higher CBF in a recanalized CTO as compared to clopidogrel, whose treated patients exhibit a lower CBF immediately after PCI with a significant increase at follow-up. The clinical value of such sustained high coronary flow should be evaluated in a larger group of patients. Clinical trial registration https://clinicaltrials.gov/ct2/show/NCT02211066 (ClinicalTrials.gov number NCT02211066 ).

La Brucelosis es una enfermedad infectocontagiosa, aguda o crónica, que afecta tanto a los animales como al hombre, causada por bacterias del género Brucella. El objetivo de la presenta investigación fue determinar la seroprevalencia de anticuerpos de brucelosis en caprinocultores y su ganado caprino en ejidos de la Comarca Lagunera. Se obtuvieron 90 muestras de suero de caprinocultores a las que se les proceso la prueba rosa de bengala como prueba tamiz, aglutinación estándar y 2-Mercaptoetanol en microplaca. Se obtuvieron 5737 muestras de suero de cabras y se realizó la prueba rosa de bengala. En caprinocultores se obtuvo una seroprevalencia general del 11%, la más elevada fue en el ejido Banco Nacional con 4.4%, predomino el género masculino y el rango de edad de 30-39 años. La seroprevalencia fue de 20.2% en cabras. La correlación entre la seroprevalencia humana y caprina fue r=0.8732; p˂0.01. Se concluyó que la seroprevalencia obtenida en caprinocultores fue superior a la seroprevalencia del Estado de Durango de 4.79% reportada en el año 2009. La seroprevalencia de brucelosis en ganado caprino es alta y existe en diez de los doce ejidos analizados. Se obtuvo una correlación altamente significativa entre la brucelosis humana y caprina.

Background:To date, there is no data on switching to dual pathway inhibition (DPI) patients who have completed a guideline-recommended dual antiplatelet therapy (DAPT) regimen. Objectives: To assess the feasibility of switching from DAPT to DPI and to compare the pharmacodynamic (PD) profiles of these treatments. Methods: This was a prospective, randomized, PD study conducted in 90 patients with chronic coronary syndrome (CCS) on DAPT with aspirin (81mg/qd) plus a P2Y12 inhibitor [clopidogrel (75 mg/qd; n=30), ticagrelor (90mg/bid; n=30), or prasugrel (10mg/qd; n=30)]. Patients in each cohort were randomized to maintain DAPT or switch to DPI (aspirin 81mg/qd plus rivaroxaban 2.5mg/bid). PD assessments included: VerifyNow P2Y12 reaction units; light transmittance aggregometry following stimuli with adenosine diphosphate (ADP), tissue factor (TF), and a combination of collagen, ADP, and TF (CATF, maximum platelet aggregation %); thrombin generation (TG). Assays were performed at baseline and 30 days post-randomization. Results: Switching from DAPT to DPI occurred without major side effects. DAPT was associated with enhanced P2Y12 inhibition, while DPI with reduced TG. Platelet-mediated global thrombogenicity (primary endpoint) showed no differences between DAPT and DPI in the ticagrelor (14.5% [0.0–63.0] vs. 20.0% [0.0–70.0]; p=0.477) and prasugrel (20.0% [0.0–66.0] vs. 4.0% [0.0–70.0]; p=0.482), but not clopidogrel (27.0% [0.0–68.0] vs. 53.0% [0.0–81.0]; p=0.011), cohorts. Conclusion: In patients with CCS, switching from different DAPT regimens to DPI was feasible, showing enhanced P2Y12 inhibition with DAPT and reduced TG with DPI, with no differences in platelet-mediated global thrombogenicity between DPI and ticagrelor- and prasugrel, but not clopidogrel-, based DAPT.