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Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy of the bile ducts within the liver characterized by high levels of genetic heterogeneity. In the context of such genetic variability, determining which oncogenic mutations drive ICC growth has been difficult, and developing modes of patient stratification and targeted therapies remains challenging. Here we model the interactions between rare mutations with more common driver genes and combine in silico analysis of patient data with highly multiplexed in vivo CRISPR-spCas9 screens to perform a functional in vivo study into the role genetic heterogeneity plays in driving ICC. Novel tumor suppressors were uncovered, which, when lost, cooperate with the RAS oncoprotein to drive ICC growth. Focusing on a set of driver mutations that interact with KRAS to initiate aggressive, sarcomatoid-type ICC revealed that tumor growth relies on Wnt and PI3K signaling. Pharmacologic coinhibition of Wnt and PI3K in vivo impeded ICC growth regardless of mutational profile. Therefore, Wnt and PI3K activity should be considered as a signature by which patients can be stratified for treatment independent of tumor genotype, and inhibitors of these pathways should be levied to treat ICC.Significance:This work shows that, despite significant genetic heterogeneity, intrahepatic cholangiocarcinoma relies on a limited number of signaling pathways to grow, suggesting common therapeutic vulnerabilities across patients.

Background: GD is a condition in which a woman develops glucose intolerance at any time during pregnancy and may or may not resolve at the end of pregnancy. Metformin, from the group of biguanides, is considered an alternative management of gestational diabetes, included in the list of essential medicines by the OMS. Methodology: A narrative review was carried out through various databases from March 2018 to September 2021; the search and selection of articles was carried out in journals indexed in English and Spanish. The following keywords were used: metformin, macrosomia, gestational diabetes. Results: The present review offers pathophysiological measures, complications, pharmacological therapy, for a better approach in perinatals in patients with gestational diabetes. Conclusion: With the results observed, it should be noted that metformin is viable for the management of patients with gestational diabetes.

Este trabajo colectivo, titulado La musicología en la formación universitaria: Investigar para comprender contribuye a la labor de divulgación del conocimiento y experiencias pedagógicas de una comunidad académica dedicada a la investigación de la educación musical, la cual se ha ido fortaleciendo y enriqueciendo a través del diálogo en los distintos encuentros propiciados por los integrantes del Cuerpo Académico (CA) consolidado UAA-CA-117, Educación y Conocimiento de la Música, quienes desde 2016, desarrollan dos líneas de investigación orientadas a la comprensión de los procesos de conocimiento y producción musicales y de los procesos de enseñanza y aprendizaje.

Liver transplantation is the only curative option for patients with end-stage liver disease. Despite improvements in surgical techniques, nonanastomotic strictures (characterized by the progressive loss of biliary tract architecture) continue to occur after liver transplantation, negatively affecting liver function and frequently leading to graft loss and retransplantation. To study the biological effects of organ preservation before liver transplantation, we generated murine models that recapitulate liver procurement and static cold storage. In these models, we explored the response of cholangiocytes and hepatocytes to cold storage, focusing on responses that affect liver regeneration, including DNA damage, apoptosis, and cellular senescence. We show that biliary senescence was induced during organ retrieval and exacerbated during static cold storage, resulting in impaired biliary regeneration. We identified decoy receptor 2 (DCR2)–dependent responses in cholangiocytes and hepatocytes, which differentially affected the outcome of those populations during cold storage. Moreover, CRISPR-mediated DCR2 knockdown in vitro increased cholangiocyte proliferation and decreased cellular senescence but had the opposite effect in hepatocytes. Using the p21KO model to inhibit senescence onset, we showed that biliary tract architecture was better preserved during cold storage. Similar results were achieved by administering senolytic ABT737 to mice before procurement. Last, we perfused senolytics into discarded human donor livers and showed that biliary architecture and regenerative capacities were better preserved. Our results indicate that cholangiocytes are susceptible to senescence and identify the use of senolytics and the combination of senotherapies and machine-perfusion preservation to prevent this phenotype and reduce the incidence of biliary injury after transplantation., This work was supported by the UK Medical Research MRC (MR/K017047/1) (to S.J.F.), the Computational and Chemical Biology of Stem Cell Niche (MR/L012766/1) (to S.J.F.), the UK Regenerative Medicine Platform (MR/K026666/1) (to S.J.F.), and the Wellcome Trust Institutional Translational Partnership Award (WT iTPA) (to S.F.-G.). J.M.B. was supported by the Spanish Carlos III Health Institute (ISCIII) (PI15/01132, PI18/01075, and Miguel Servet Program CON14/00129 and CPII19/00008) cofinanced by “Fondo Europeo de Desarrollo Regional” (FEDER); “Instituto de Salud Carlos III” (CIBERehd), Spain; “Euskadi RIS3” (2019222054 and 2020333010); and the Department of Industry of the Basque Country (Elkartek: KK-2020/00008). This research was funded in whole or in part by The Wellcome Trust (grant number 209710/Z/17/Z), a cOAlition S organization.

Aims To non-invasively characterize, by means of late gadolinium enhancement cardiac magnetic resonance (LGE-CMR), scar differences, and potential variables associated with ventricular tachycardia (VT) occurrence in chronic post-myocardial infarction (MI) patients. Methods and results A case–control study was designed through retrospective LGE-CMR data analysis of chronic post-MI patients (i) consecutively referred for VT substrate ablation after a first VT episode (n = 66) and (ii) from a control group (n = 84) with no arrhythmia evidence. The myocardium was characterized differentiating core, border zone (BZ), and BZ channels (BZCs) using the ADAS 3D post-processing imaging platform. Clinical and scar characteristics, including a novel parameter, the BZC mass, were compared between both groups. One hundred and fifty post-MI patients were included. Four multivariable Cox proportional hazards regression models were created for total scar mass, BZ mass, core mass, and BZC mass, adjusting them by age, sex, and left ventricular ejection fraction (LVEF). A cut-off of 5.15 g of BZC mass identified the cases with 92.4% sensitivity and 86.9% specificity [area under the ROC curve (AUC) 0.93 (0.89–0.97); P Conclusions The mass of BZC is the strongest independent variable associated with the occurrence of sustained monomorphic ventricular tachycardia in post-MI patients after adjustment for age, sex, and LVEF. Border zone channel mass measurement could permit a more accurate VT risk stratification than LVEF in chronic post-MI patients.

Background Pacemapping (PM) is a useful maneuver for aiding premature ventricular complex (PVC) ablation. Its standalone clinical value is still to be defined. Objectives The purpose of this study was to analyze the efficacy of a predefined PM protocol for low-burden PVC ablation, regardless of their site of origin (SOO) and the presence of structural heart disease. Methods This was a prospective, nonrandomized, multicenter study. The PM protocol was performed when 94% correlation, and 3 radiofreqency (RF) applications were delivered. Results Of 185 patients, 105 (57%) underwent activation mapping, 60 (32%) were PM-guided, and 20 (11%) were canceled due to absence of PVCs. Baseline QRS, PVC burden, and outflow tract origin were independent predictors of PM-guided ablation. A higher proportion of right ventricular outflow tract SOO in the PM group (52% vs 40%; P = .03) was observed. Mean target area was 0.6 ± 0.9 cm2. Mean 10-ms isochronal area in local activation time (LAT)-guided procedures was higher (1.7 ± 2.3 cm2; P Conclusion When LAT mapping is precluded, application of a PM-guided ablation protocol directed to >94% matching correlation target area is a more efficient alternative with comparable clinical results.

Funder: RCUK | Medical Research Council (MRC); doi: https://doi.org/10.13039/501100000265, Funder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/501100000289, Funder: Wellcome Trust (Wellcome); doi: https://doi.org/10.13039/100004440, Funder: Barts Charity, The MYC oncogene is a potent driver of growth and proliferation but also sensitises cells to apoptosis, which limits its oncogenic potential. MYC induces several biosynthetic programmes and primary cells overexpressing MYC are highly sensitive to glutamine withdrawal suggesting that MYC-induced sensitisation to apoptosis may be due to imbalance of metabolic/energetic supply and demand. Here we show that MYC elevates global transcription and translation, even in the absence of glutamine, revealing metabolic demand without corresponding supply. Glutamine withdrawal from MRC-5 fibroblasts depletes key tricarboxylic acid (TCA) cycle metabolites and, in combination with MYC activation, leads to AMP accumulation and nucleotide catabolism indicative of energetic stress. Further analyses reveal that glutamine supports viability through TCA cycle energetics rather than asparagine biosynthesis and that TCA cycle inhibition confers tumour suppression on MYC-driven lymphoma in vivo. In summary, glutamine supports the viability of MYC-overexpressing cells through an energetic rather than a biosynthetic mechanism.

Several classification systems have been developed to support orthopedic surgeons regarding diagnostic, treatment, or prognostic outcomes of distal radius fracture (DRF). However, the best classification system for this fracture remains controversial. We aimed to identify the reliability of three different DRF classifications among orthopedists in training (medical residents).Orthopedic residents (n = 22) evaluated thirty cases of DRF in anteroposterior and lateral projections in three different periods (0, 6, 12 months). Each radiography was sorted with three different classifications: Frykman, AO/OTA, and Jupiter-Fernandez. All assessments were blinded to the investigators. The inter- and intra-observer reliability was evaluated using the Cohen's kappa coefficient. An additional analysis was performed for a simpler sub-classification of the AO/OTA (27, 9, or 3 groups).Inter-observer agreement for AO/OTA, Frykman, and Jupiter-Fernandez classifications was slight (k = 0.15), fair (k = 0.31), and fair (k = 0.30), respectively. Intra-observer agreement showed similar results: AO/OTA, k = 0.14; Frykman, k = 0.28; and Jupiter-Fernandez, k = 0.28. When the AO/OTA classification was simplified (9 or 3 descriptions), the inter-observer agreement improved from slight (k = 0.16) to fair (k = 0.21 and k = 0.30, respectively). A similar improvement from slight (k = 0.14) to fair (k = 0.32 and k = 0.21) was detected for intra-observer agreement.The more complex the DRF classification system, the more complex is to reach reliable inter- and intra-observer agreements between orthopedic trainees. Senior residents did not necessarily show greater kappa values in DRF classifications.

To evaluate the efficacy of arthrotomy, when compared with arthroscopy, in the treatment of adults with septic arthritis of any joint. MEDLINE, EMBASE, and Scopus were searched to identify studies comparing arthrotomy and arthroscopy as therapeutic approaches in patients with septic arthritis of any joint. The main outcome was the re-infection rate. A meta-analysis was performed using the generic inverse variance method with random or fixed effects model depending on heterogeneity between studies. Heterogeneity was tested with the I2 statistic index. Twenty studies with 10,249 patients treated by arthrotomy or arthroscopy were evaluated. We observed a significant lower risk of re-infection (odds ratio [OR], 1.35 [95% CI, 1.16–1.58]; p = 0.0002) and complications (OR, 1.32 [95% CI, 1.12–1.55]; p = 0.001) rate as well as less hospital stay (mean difference [MD], 0.57 days [95% CI, 0.10–1.05]; p = 0.02) favouring arthroscopic intervention. The subanalysis indicated that patients with knee (OR, 1.50 [95% CI, 1.17–1.92]; p = 0.001) and shoulder (OR, 1.24 [95% CI, 1.00–1.53]; p = 0.04) septic arthritis intervened by arthrotomy had a higher risk of re-infection. A lower number of hospitalization days (MD, 0.89 days [95% CI, 0.31–1.47]; p = 0.003) and a lower risk for complications (OR, 1.26 [95% CI, 1.04–1.52]; p = 0.02) were observed in patients treated with arthroscopy after septic knee arthritis. Available evidence suggests that patients with septic arthritis of the knee and shoulder treated by arthroscopy have less risk of re-infection than those treated by arthrotomy. The quality of the body of evidence is still insufficient to reach reliable conclusions. CRD42020176044. Date registration: April 28, 2020.

The following article intends the description of the religious and intellectual environment in prerevo-lutionary America. It is divided into two main sec-tions: (1) a religious one where I will cover the most significant elements, and the ideological context of what was the most decisive cultural force in the formation of the new country ?Puritanism?; and (2) another that succinctly describes the particular shape that enlightened thought acquired in that part of the British Empire.A description of eighteenth-century Puritan North America requires a closer look at the ver-sion of Calvinism prevalent in the Northeastern seaboard, and therein to the cultural phenomenon of religious revivalism. Now connected to these variables lie a series of theological conceptions that shaped Puritan belief and practice in manifold ways, and that will be covered in the first section of this work: Arminianism, Antinomianism, Millen-nialism, and Religious Enthusiasm, among others.

Background: Whether the sex factor influences the benefit of the implantable cardioverter-defibrillator (ICD) for the prevention of sudden death remains a subject of debate. Using a prospective reg...

RESUMEN La abundancia como parámetro demográfico es un elemento importante de la dinámica poblacional, permitiendo hacer comparaciones espaciotemporales y evaluar el estado de salud de las especies. Los objetivos de este trabajo fueron conocer la estructura temporal de un ensamble de anuros del Chaco Serrano en el centro-oeste de Argentina e identificar la influencia de factores climáticos sobre esos parámetros. Se realizaron catorce muestreos desde octubre de 2012 a febrero de 2015, agrupándose en estaciones seca y lluviosa. La abundancia de especies se analizó mediante: 1) abundancias medias, con análisis de varianza factorial y 2) proporciones, como frecuencias de ocurrencia, a partir de pruebas Chi cuadrado. Se realizó un análisis de redundancia relacionando la abundancia, estaciones, y variables ambientales. En ambas estaciones Rhinella arenarum arenarum fue la especie más abundante, seguida por Pleurodema tucumanum y Leptodactylus luctator. Se hallaron diferencias significativas en la abundancia, entre estaciones y sexos, existiendo interacciones significativas entre estos factores. En la estación seca R. arenarum arenarum y L. luctator presentaron diferencias en las proporciones de sexos, mientras que en la estación lluviosa solo P. tucumanum exhibió diferentes frecuencias de ocurrencia entre machos y hembras. La temperatura mínima y las precipitaciones influyeron significativamente en la abundancia de P. tucumanum. No se encontraron influencias climáticas para las otras especies. Los resultados de esta investigación contribuyen a entender la estructura de ensamblajes de anuros del Chaco, sugiriendo que las poblaciones son fluctuantes en el tiempo y que pueden depender, en algunas especies, de factores abióticos como temperatura y precipitaciones. ABSTRACT Abundance as a demographic parameter is an important part of population dynamics, allowing space-time comparisons and evaluating the health status of species. This work aimed to know the temporal structure of an anuran assembly from Chaco Serrano in central-western Argentina and to identify the influence of climatic factors on those parameters. 14 samplings were carried out from October 2012 to February 2015. Samplings were grouped into dry and rainy seasons. The abundance of each species was analyzed by: 1) mean abundances, with factorial analysis of variance and 2) proportions, as frequencies of occurrence, from Chisquare tests. Redundancy analysis was performed to relate abundance, seasons, and environmental variables. In both seasons Rhinella arenarum arenarum was the most abundant species, followed by Pleurodema tucumanum and Leptodactylus luctator. Significant differences were found in species abundance, between seasons, and between sexes, with significant interactions between these factors. In the dry season, R. arenarum arenarum and L. luctator showed differences in sex ratios, whereas in the rainy season only P. tucumanum exhibited different frequencies between males and females. The minimum temperature and the rainfall proved to be significant variables in P. tucumanum abundance. No climatic influences were found for the other species. The results of this research contribute to understanding the Chaco anuran assemblage structure, suggesting that populations fluctuate over time and it may depend, in some species, on abiotic factors such as temperature and rainfall.

To compare the effects of oral e-aminocaproic acid (EACA) as a hemostatic agent versus the use of oral tranexamic acid (TXA) administered in multiple doses pre and postsurgery in patients undergoing elective primary total hip arthroplasty (THA). We enrolled 102 patients that were randomly divided into two groups: received three oral doses of EACA (2000 mg per dose) or three oral doses of TXA (1300 mg per dose). The medication was given according to the following schedule: 2 h before surgery and 6 and 12 h after surgery. The variables analyzed to compare the effectiveness of the hemostatic agents were total blood loss, hidden blood loss, external blood loss, transfusion rate, intraoperative blood loss, decreases in hemoglobin and hematocrit values, surgical drainage output, visual analog scale, and surgical complications. There were no significant differences between any of the study variables for the group receiving oral TXA and the group receiving oral EACA (P > 0.05). Our study showed that the use of oral EACA was similar to its counterpart TXA regarding the evaluated parameters. TXA did not have superior blood conservation effects, safety profile, or differences in functional scales compared with EACA in THA. We consider the use of multiple oral doses of aminocaproic acid at the selected dose to be effective as a standard protocol to achieve less blood loss and a lower rate of transfusion and adverse events related to the medication in patients undergoing a THA.

En adultos mayores, la ancylostomiasis tiene manifestaciones básicas como pérdida del apetito y masa muscular, evacuación excesiva, debilidad y otras que hacen propenso al adulto mayor a un estado de fragilidad, un tipo de síndrome de fallo multiorgánico crónico, donde interviene la disfunción de diversos sistemas. Este agravante fundamenta el objetivo de la presente investigación, centrado en identificar el comportamiento de los criterios clínicos, funcionales, mentales y sociodemográficos en la evaluación geriátrica del síndrome de fragilidad en adultos mayores parasitados por Ancylostoma spp. en el cantón Santiago de Píllaro. La muestra resultó integrada por un total de 102 adultos mayores a 65 años. Mediante la revisión de las historias clínicas y la aplicación de una encuesta a los participantes, se evaluó el comportamiento de los criterios sociodemográficos, médicos, funcionales, mentales y de comorbilidad asociada. Los datos obtenidos fueron procesados estadísticamente mediante análisis bivariado y regresión logística múltiple. Los factores estadísticamente asociados a la fragilidad fueron el sexo femenino (p= 0,003, IC 95% ,LI= 1,564 y LS= 8,950), los bajos ingresos económicos (p= 0,011, IC 95%: LI= 1,786 y LS= 7,433), la polifarmacia (p= 0,006, IC 95%: LI= 2,452 y LS= 14,415) ), las evacuaciones frecuentes (p=0,009, con IC95%: LI=2,704 y LS=7,536) y las afecciones bucodentales (p= 0,004, IC 95%: LI= 1,895 y LS= 6,572), por lo que se justifica la elaboración de estrategias y acciones de salud que minimicen los efectos del estado de fragilidad en la población estudiada

Las cooperativas son un pilar fundamental de la economía solidaria y desempeñan una función importante dentro del sistema económico como generadoras de empleo. El trabajo que presentamos tiene como objetivo el análisis de los factores determinantes de la eficiencia de las Cooperativas Multiactivas sin Sección de Ahorro de Colombia durante el período 2003-2015. El análisis se basa en la selección de aquellos factores que según la literatura explican perfectamente la situación de las cooperativas, así como la selección de la metodología de la técnica no paramétrica DEA en dos etapas, propuesto por Simar y Wilson. Como inputs se sugieren el número de asociados y de empleados, gastos de administración, capital social y los ingresos operacionales. Los excedentes operacionales constituyen el output considerado. Los resultados indican una eficiencia técnica del 50% en promedio. Finalmente, es la variable aumento en el número de asociados el principal factor determinante de la eficiencia

Cellular senescence is a stress response characterised by a permanent cell cycle arrest and a proinflammatory secretome. In addition to its tumour suppressor role, senescence is involved in ageing and promotes many disease processes such as cancer, type 2 diabetes, osteoarthritis, and SARS-CoV-2 infection. There is a growing interest in therapies based on targeted elimination of senescent cells, yet so far only a few such senolytics are known, partly due to the poor grasp of the molecular mechanisms that control the senescence survival programme. Here we report a highly effective machine learning pipeline for the discovery of senolytic compounds. Using solely published data, we trained machine learning algorithms to classify compounds according to their senolytic action. Models were trained on as few as 58 known senolytics against a background of FDA-approved compounds or in late-stage clinical development (2,523 in total). We computationally screened various chemical libraries and singled out top candidates for validation in human lung fibroblasts (IMR90) and lung adenocarcinoma (A549) cell lines. This led to the discovery of three novel senolytics: ginkgetin, oleandrin and periplocin, with potency comparable to current senolytics and a several hundred-fold reduction in experimental screening costs. Our work demonstrates that machine learning can take maximum advantage of existing drug screening data, paving the way for new open science approaches to drug discovery for senescence-associated diseases.

Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy of the bile ducts within the liver characterized by high levels of genetic heterogeneity. In the context of such genetic variability, determining which oncogenic mutations drive ICC growth has been difficult, and developing modes of patient stratification and targeted therapies remains challenging. Here we model the interactions between rare mutations with more common driver genes and combine in silico analysis of patient data with highly multiplexed in vivo CRISPR-spCas9 screens to perform a functional in vivo study into the role genetic heterogeneity plays in driving ICC. Novel tumor suppressors were uncovered, which, when lost, cooperate with the RAS oncoprotein to drive ICC growth. Focusing on a set of driver mutations that interact with KRAS to initiate aggressive, sarcomatoid-type ICC revealed that tumor growth relies on Wnt and PI3K signaling. Pharmacologic coinhibition of Wnt and PI3K in vivo impeded ICC growth regardless of mutational profile. Therefore, Wnt and PI3K activity should be considered as a signature by which patients can be stratified for treatment independent of tumor genotype, and inhibitors of these pathways should be levied to treat ICC. Significance: This work shows that, despite significant genetic heterogeneity, intrahepatic cholangiocarcinoma relies on a limited number of signaling pathways to grow, suggesting common therapeutic vulnerabilities across patients.

Targeting early-stage lung cancer is vital to improve survival. However, the mechanisms and components of the early tumor suppressor response in lung cancer are not well understood. In this report, we study the role of Toll-like receptor 2 (TLR2), a regulator of oncogene-induced senescence, which is a key tumor suppressor response in premalignancy. Using human lung cancer samples and genetically engineered mouse models, we show that TLR2 is active early in lung tumorigenesis, where it correlates with improved survival and clinical regression. Mechanistically, TLR2 impairs early lung cancer progression via activation of cell intrinsic cell cycle arrest pathways and the proinflammatory senescence-associated secretory phenotype (SASP). The SASP regulates non-cell autonomous anti-tumor responses, such as immune surveillance of premalignant cells, and we observe impaired myeloid cell recruitment to lung tumors after Tlr2 loss. Last, we show that administration of a TLR2 agonist reduces lung tumor growth, highlighting TLR2 as a possible therapeutic target., F.R.M. is funded by a Wellcome Trust clinical research fellowship through the Edinburgh Clinical Academic Track (ECAT) program (203913/Z/16/Z), a Wellcome Trust-ISSF3 award (IS3-R1.07 20/21), and a Wellcome Trust iTPA award (209710/Z/17/Z). J.C.A. core lab funding was received from Cancer Research UK (C47559/A16243, Training and Career Development Board – Career Development Fellowship), the University of Edinburgh (Chancellor’s Fellowship), and the Ministry of Science and Innovation of the Government of Spain (Proyecto PID2020-117860GB-100 financiado por MCIN/AEI/10.13039/501100011033). S.W. is supported by a Cancer Research UK senior fellowship (A29576). J.C. is supported by a Wellcome Trust clinical lectureship through the ECAT program (203913/Z/16/Z). M.M. is supported by a CRUK Edinburgh Centre Award (C157/A25140). S.V. and J.F.P. are funded by National Institute on Aging (NIA) grants (R01AG 68048-1 and UG3CA 268103-1).

We perform trajectory-based simulations of the vibrational predissociation of the ArBr

Background: Plantar fasciitis is the most common cause of heel pain, and injection therapies are part of the treatment modalities. This study aimed to compare 2 intralesional injection therapies for plantar fasciitis: corticosteroid and botulinum toxin A, compared with a third control group using a local anesthetic. The clinical evolution, as well as changes in the thickness of the plantar fascia and ankle dorsiflexion, was evaluated. Methods: A randomized, controlled, double-blind trial design was used. Patients were divided into 3 groups: group 1, anesthetic only; group 2, corticosteroid; and group 3, botulinum toxin A (BoNT-A). We used an ultrasonographic evaluation to measure the plantar fascia thickness. The results were evaluated using the Maryland Foot Score and a 10-cm visual analog scale. Clinical scores were recorded at the beginning of the study, at 2 weeks, and at 1, 3, and 6 months. We evaluated 78 patients for study eligibility. The 3 intervention groups were homogeneous. Results: All patients showed better clinical outcomes compared with their initial evaluations, without differences between groups at the end of follow-up. The thickness of plantar fascia diminished at the final evaluation, and ankle dorsiflexion was better compared with the initial values without difference between treatment groups. Conclusion: Considering all the evaluated outcomes, no significant differences between treatment groups were observed. The pain relief and functional improvement obtained with the different treatments was maintained during the 6-month follow-up. Level of Evidence: Level I, therapeutic study.

Las Instituciones de Educación Superior, son empresas que brindan servicios educativos, ofreciendo programas académicos a nivel tecnológico, universitario, de formación continua y posgrados, diseñados para atender necesidades sentidas del sector social y productivo, mediante un proceso integral. En el desarrollo del presente escrito, se realizó una revisión descriptiva sobre los distintos métodos estadísticos usados para determinar las causas que han generado el problema de deserción escolar y el bajo rendimiento académico de los estudiantes, lo cual proporciona al lector una puesta al día sobre conceptos y herramientas de gran interés, para establecer acciones de precaución y mejora continua en los procesos académicos de enseñanza aprendizaje.

Crítica de la razón pura: una antología hispanoamericana, realizada por Luis Eduardo Hoyos y P. Stepanenko. En ésta es posible en- contrar una serie de enfoques muy actuales, que permiten al lector en lengua española tener un primer acer- camiento —complejo y detallado— a las partes medulares del pensamiento filosófico de Kant. El libro cuenta con once artículos, los cuales abordan y desarrollan nue- vos enfoques sobre temas kantianos clásicos. En algunos casos, los autores muestran ciertos errores e imprecisio- nes en los que Kant —desafortuna- damente— incurrió al momento de moldear su proyecto filosófico, como lo comprueban las aproximaciones críticas que realizan en sus trabajos.

Aim To determine the effectiveness of a hydrophobic dressing (Cutimed Sorbact® ) against a silver dressing (Aquacel® Ag Extra) in the level of colonization of chronic venous leg ulcers. The secondary endpoints are health-related quality of life, level of pain, and time to complete healing. Design Open randomized controlled trial, with blinded endpoint. Methods Patients with chronic venous leg ulcers with signs of critical colonization will be randomized in a concealed sequence using computer software to receive one of the alternative dressings. A total of 204 participants recruited in Primary Health Care and nursing homes will be necessary to assure statistical power. Measures will include sociodemographic variables, wound-related variables (area, exudate, and time to healing), level of pain, adverse effects, and health-related quality of life. Smear samples will be collected from the ulcers and will be subject to DNA-typing technique through polymerase chain reaction to obtain the level of colony-forming units. Measures will be collected at baseline, 4, 8, and 12 weeks. Discussion Elevated levels of microorganisms prevent wound healing and favour its chronification. The main target when colonization is present is to reduce the bacterial load to levels that promote immune system mobilization. Hydrophobic dressings prevent the formation of biofilm in the wound by means of physical effect, so that the possibility of antimicrobial resistance is significantly reduced. Impact Current evidence about the effectiveness of dressings to minimize venous leg ulcers colonization is very limited. Previous studies have important methodological flaws. This study will permit to obtain the effectiveness of hydrophobic dressings against silver dressings with a robust design based on conditions of routine clinical practice in Primary Health Care and nursing homes.

Atrial fibrillation is the most prevalent arrhythmia in the world population. Despite the use of antiarrhythmics, it is difficult to control clinically, causing symptoms and mainly generating risk of a thromboembolic event. Since 1998, by means of radiofrequency ablation, the treatment of atrial fibrillation has completely changed, but together with this important evolution complications from this ablative treatment technique have also started. In addition to the pulmonary vein stenosis caused by the ablation and later corrected with the change in the technique, atrioesophageal fistulas appeared due to the application of radiofrequency in the posterior wall of the left atrium. This wall is very close (0.5 cm onaverage) to the esophagus, which facilitates the formation of the fistula that leads to the death of almost 100% of the affected patients, despite the various treatment measurements already developed. To avoid this serious complication, several authors have created techniques to protect the esophagus including its mechanical deviation to a region opposite to the radiofrequency application, taking advantage of its mobility and easiness of handling. The mechanical deviation of the esophagus has proven to be the simplest, cheapest and most efficient way to protect this organ from radiofrequency thermal damage during atrial fibrillation ablation.

A fibrilação atrial é a arritmia de maior prevalência na população mundial. Apesar do uso de antiarrítmicos, é de difícil controle clínico, ocasionando sintomas e principalmente gerando risco de um evento tromboembólico. A partir de 1998, por meio da ablação por radiofrequência, o tratamento da fibrilação atrial mudou completamente, porém junto a essa importante evolução também iniciaram as complicações advindas dessa técnica de tratamento ablativo. Além das estenoses das veias pulmonares causadas pela ablação e posteriormente corrigidas com a mudança da técnica, surgiram as fístulas átrio-esofágicas, devido à aplicação de radiofrequência na parede posterior do átrio esquerdo. Esta parede está bem próxima (0,5 cm em média) do esôfago, facilitando a formação da fístula que leva à morte quase 100% dos pacientes acometidos, apesar das diversas medidas de tratamento já desenvolvidas. Para evitar essa grave complicação, vários autores criaram técnicas para proteger o esôfago incluindo seu desvio mecânico para uma região oposta à da aplicação de radiofrequência, aproveitando a sua mobilidade e facilidadede abordagem. O desvio mecânico do esôfago tem se mostrado a forma mais simples, barata e eficiente de proteger esse órgão da lesão térmica da radiofrequência durante a ablação da fibrilação atrial.

Resumen En el ultimo ano se han producido importantes avances en el conocimiento y el diagnostico de las arritmias cardiacas, asi como en nuevas opciones de tratamiento. En este articulo pretendemos realizar un resumen de los trabajos del ano 2019 con interes para los electrofisiologos, principalmente centrados en el tratamiento intervencionista y los avances en dispositivos electronicos implantables.

To compare the effects of platelet-rich plasma (PRP) injection versus placebo (saline injection) on pain and joint function in lateral epicondylitis in randomized placebo-controlled trials. Randomized controlled trials that evaluated pain (visual analog scale [VAS] and patient-rated tennis elbow evaluation [PRTEE]) and/or functional improvement (PRTEE; disability of the arm, shoulder, and hand [DASH]; and Roles–Maudsley score [RMS]) in patients diagnosed with lateral epicondylitis and compared PRP with placebo injections were considered. The MEDLINE, EMBASE, Web of Science, and Scopus databases were searched from inception to October 2019. The assessment of bias was performed using the Cochrane Risk of Bias Tool version 1. The meta-analysis was conducted with a random effects model and generic inverse variance method. Five trials involving a total of 276 individuals were included. They used a parallel study design and saline solution as placebo. The mean age of participants was 48.0 ± 9.3 years. Follow-up varied from 2 months to 1 year. No significant changes were noted for pain (standardized mean difference [SMD], − 0.51 [95% confidence interval (CI), − 1.32 to − 0.30]) nor functional scores (SMD, − 0.07 [95% CI, − 0.46 to 0.33]) between PRP and placebo injections. The most frequent adverse reaction reported in two of the five studies was transient post-injection pain for a few days (from 16 to 20% in the PRP group and from 8 to 16% in the placebo group). PRP injection was not superior to placebo for relieving pain and joint functionality in chronic lateral epicondylitis. However, patients reported improvement after both interventions in such clinical parameters. Further randomized trials are required to determine whether PRP injection is clinically more effective than placebo (saline injection).

Background: Lateral epicondylitis, or tennis elbow, is a painful degenerative disorder that commonly occurs in adults between 40 and 60 years of age. Normal saline (NS) injections have been used as placebo through a large number of randomized controlled trials (RCTs) focused on the treatment of lateral epicondylitis. Purpose: This meta-analysis of RCTs aimed to assess the therapeutic effect of NS injections on lateral epicondylitis symptoms and compare results with established minimal clinically important difference criteria. Study Design: Systematic review and meta-analysis. Methods: MEDLINE, Embase, Web of Science, and Scopus databases were searched for clinical trials reporting pain and joint function with the visual analog scale, Patient-Rated Tennis Elbow Evaluation, and Disabilities of the Arm, Shoulder and Hand in patients with lateral epicondylitis. The meta-analysis was conducted with a random effects model and generic inverse variance method. Heterogeneity was tested with the I2 statistic index. Results: A total of 15 RCTs included in this meta-analysis revealed a significant improvement in pain (mean difference, 3.61 cm [95% CI, 2.29-4.92 cm]; P < .00001; I2 = 88%; visual analog scale) and function (mean difference, 25.65 [95% CI, 13.30-37.99]; P < .0001; I2 = 82%; Patient-Rated Tennis Elbow Evaluation / Disabilities of the Arm, Shoulder and Hand) after NS injection (≥6 months). Conclusion: NS injections yielded a statistically significant and clinically meaningful improvement in pain and functional outcomes in patients with lateral epicondylitis. New research should focus on better methods to diminish the potential confounders that could lead to this effect because NS injections could mask the real effect of an active therapeutic intervention in RCT. Registration: CRD42019127547 (PROSPERO).

The vasovagal syncope is the most frequent cause of transient loss of consciousness, especially in young people without significant heart disease. The malignant cardioinhibitory form is caused by abrupt and intense vagal reflex with or without defined triggers. Refractory cases to preventive measures and pharmacological handling has been treated with definitive pacemaker implantation. Besides showing questionable results, pacemaker implantation is highly rejected by young patients. In the late 1990s, we proposed specific vagal denervation by catheter ablation and spectral mapping, for paroxysmal AF, functional bradyarrhythmias and severe cases of malignant cardioinhibitory syncope giving rise to cardioneuroablation. Recently, many authors worldwide have been reproducing the cardioneuroablation results where elimination or significant reduction of the vagal response were observed, which abolished symptoms in more than 75% of patients followed up to 14 years, without complications. Therefore, cardioneuroablation has shown to be a real therapeutic option in malignant syncope cardioinhibitory and in any exclusive vagal mediated bradyarrhythmia without the need for pacemaker implantation.

A síncope vasovagal é a causa mais frequente de perda transitória de consciência, especialmente em jovens sem doença cardíaca significativa. A forma cardioinibitória maligna é causada por reflexo vagal abrupto e intenso com ou sem gatilhos definidos. Casos refratários a medidas preventivas e manuseio farmacológico foram tratados com implante definitivo de marcapasso. Além de apresentar resultados questionáveis, o implante de marcapasso é altamente rejeitado por pacientes jovens. No final dos anos 1990, propusemos uma denervação vagal específica por ablação do cateter e mapeamento espectral para FA paroxística, bradiarritmias funcionais e casos graves de síncope cardioinibitória maligna dando origem à cardioneuroablação. Recentemente, muitos autores em todo o mundo vêm reproduzindo os resultados da cardioneuroablação, onde se observou eliminação ou redução significativa da resposta vagal, o que aboliu sintomas em mais de 75% dos pacientes acompanhados por até 14 anos, sem complicações. Portanto a cardioneuroablação tem se mostrado uma verdadeira opção terapêutica na síncope cardioinibitória maligna e em qualquer bradiarritmia vagal exclusiva mediada sem a necessidade de implante de marcapasso.

Cytoplasmic recognition of microbial lipopolysaccharides (LPS) in human cells is elicited by the caspase-4 and caspase-5 noncanonical inflammasomes, which induce a form of inflammatory cell death termed pyroptosis. Here we show that LPS-mediated activation of caspase-4 also induces a stress response promoting cellular senescence, which is dependent on the caspase-4 substrate gasdermin-D and the tumor suppressor p53. Furthermore, we found that the caspase-4 noncanonical inflammasome is induced and assembled in response to oncogenic RAS signaling during oncogene-induced senescence (OIS). Moreover, targeting caspase-4 expression in OIS showed its critical role in the senescence-associated secretory phenotype and the cell cycle arrest induced in cellular senescence. Finally, we observed that caspase-4 induction occurs in vivo in mouse models of tumor suppression and ageing. Altogether, we are showing that cellular senescence is induced by cytoplasmic LPS recognition by the noncanonical inflammasome and that this pathway is conserved in the cellular response to oncogenic stress., This work was funded by Cancer Research UK (CRUK) (C47559/A16243 Training & Career Development Board - Career Development Fellowship), the University of Edinburgh Chancellor’s Fellowship R42576 MRC, and the Ministry of Science and Innovation of the Government of Spain (Proyecto PID2020-117860GB-I00 financiado por MCIN/ AEI /10.13039/501100011033). J.C.A. was supported by CRUK, the University of Edinburgh and is supported by the Spanish National Research Council (CSIC). P.H., I.F.D and N.T. were funded by the University of Edinburgh. A.Q. was funded by CRUK. J.F.P and A.B.L. are funded by NIH grants: 1R01AG068048-01; P01 AG062413; 1UG3 CA268103-01. J.B. was funded by BBSRC (BB/K017314/1). V.S-B is supported by funding from the University of Edinburgh and Medical Research Council (MC_UU_00009/2). F.R.M is funded by a Wellcome Trust Clinical Research Fellowship through the Edinburgh Clinical Academic Track (ECAT) (203913/Z/16/Z). M.M. was supported by CRUK Edinburgh Centre Award (C157/A25140). V.G.B. is funded by CRUK (C157/A24837) and the University of Edinburgh.

Background: Isolated ACL lesions can occur in up to 44.5% of sports patients and its association with a meniscal injury can be 30-80%. Objective: The aim of our study was to evaluate and compare clinical function of the knee in patients with reconstruction of the ACL, with or without meniscal injury. Methods: This was a retrospective study during a four-year period of patients with ACL repaired injury. Inclusion criteria were indistinct gender, >18 years of age with a primary ACL repaired injury (with or without associated meniscal injury). The exclusion criterion were an associated knee injury (except meniscal injury), an associated fracture in the lower limb, previous knee surgery, reconstruction surgery, graft failure after 7 months, rheumatological or psychiatric disease. The Tegner Lysholm Knee Scoring Scale, the International Knee Documentation Committee (IKDC) form and a Visual Analog Scale (VAS) were applied. The patients were divided into groups, ≤1 year and >1 year of follow-up after surgery, and in ACL injury alone or ACL plus meniscal injury. Results: A total of 126 ACL injuries were analyzed. No significant difference was observed between groups in demographic data. In the patients with meniscal injury, the medial meniscus was involved in 24 (50%) cases, and the lateral meniscus 22 (46%). No difference was observed between groups in the evaluation with the Lysholm-Tegner score, IKDC and VAS. Conclusion: Patients with isolated ACL lesions or ACL lesions plus meniscal injuries, treated with partial meniscectomy, presented a similar clinical and functional evolution even after four years of treatment.