Respuesta presora al estrés como marcador pronóstico de hipertensión futura

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina. Fecha de lectura: 8 de Noviembre de 2013

El estudiante de Medicina: Un ficus en formación

Actualmente, la formación universitaria en el Grado en Medicina consta de la realización de seis años durante los cuales se adquieren una serie de conocimientos teóricos y prácticos mediante la asistencia a las prácticas clínicas en los diferentes centros asociados a las instituciones universitarias en cuestión. Concretamente la formación ofertada por la Universidad de Alcalá consta de un plan estructurado en el que la formación práctica se reduce a un sexto del total de horas invertidas para lograr alcanzar el título de graduado. Ante ello, se nos plantean una serie de preguntas ¿Son estas suficientes horas de prácticas y son aprovechadas? ¿Cómo es la realidad de las prácticas clínicas? ¿Es posible que el estudiante pueda realizar una formación adicional al currículum y disposiciones de su Grado? La realidad es que, en ocasiones, las prácticas clínicas no son aprovechadas, ya que los estudiantes se convierten en elementos decorativos del espacio sanitario como consecuencia de errores en la capacidad de integración del mismo en el equipo asistencial siendo prioritaria la asistencia al paciente sobre la formación del estudiante; así mismo, asumimos la falta de motivación, cooperación e interés por parte del estudiantado, tanto en el ámbito de las prácticas clínicas como en el de la formación humanista, investigadora y profesional. Por tanto, el estudiante de medicina ¿es un ficus en formación? Hemos pretendido abordar en el presente trabajo dicha resolución realizando una revisión de los diferentes planes de estudios de las universidades nacionales e internacionales, resaltando aquellos más llamativos.Nowadays, it takes six years to obtain a medical degree. During their time at university, the students acquire theoretical and practical knowledge through clinical rotations in partner institutions. Regarding the University of Alcalá, these rotations were reduced by one sixth in its study plan. The student is the said to have acquired the skills necessary to graduate from university. In the light of these considerations, some questions arise: Are these training hours enough? Are students being adequately trained during their clinical rotations? What is current situation of the clinical rotations? Is it feasible for the student to receive additional training outside the established study plan? The truth is, this practical training is not always helpful for the students, as the feel useless in an environment where their skills are not strengthened and used. This is due to their lack of integration in the health-care team, as patient care is of greater importance than student training. Moreover, it is also noteworthy the lack of motivation, cooperation and interest among students during their practical, humanistic, research and professional training. In order to analyze what has been said heretofore, this study is going to examine the different study plans of national and international universities, emphasizing those with the most conspicuous features

Genotype analysis of the human endostatin variant p.D104N in benign and malignant adrenocortical tumors

OBJECTIVE: Endostatin is a potent endogenous inhibitor of angiogenesis. It is derived from the proteolytic cleavage of collagen XVIII, which is encoded by the COL18A1 gene. A polymorphic COL18A1 allele encoding the functional polymorphism p.D104N impairs the activity of endostatin, resulting in a decreased ability to inhibit angiogenesis. This polymorphism has been previously analyzed in many types of cancer and has been considered a phenotype modulator in some benign and malignant tumors. However, these data are controversial, and different results have been reported for the same tumor types, such as prostate and breast cancer. The purpose of this study was to genotype the p.D104N variant in a cohort of pediatric and adult patients with adrenocortical tumors and to determine its possible association with the biological behavior of adrenocortical tumors. METHODS: DNA samples were obtained from 38 pediatric and 56 adult patients (0.6-75 yrs) with adrenocortical tumors. The DNA samples were obtained from peripheral blood, frozen tissue or paraffin-embedded tumor blocks when blood samples or fresh frozen tissue samples were unavailable. Restriction fragment length polymorphism analysis was used to genotype the patients and 150 controls. The potential associations of the p.D104N polymorphism with clinical and histopathological features and oncologic outcome (age of onset, tumor size, malignant tumor behavior, and clinical syndrome) were analyzed. RESULTS: Both the patient group and the control group were in Hardy-Weinberg equilibrium. The frequencies of the p.D104N polymorphism in the patient group were 81.9% (DD), 15.9% (DN) and 2.2% (NN). In the controls, these frequencies were 80.6%, 17.3% and 2.0%, respectively. We did not observe any association of this variant with clinical or histopathological features or oncologic outcome in our cohort of pediatric and adult patients with adrenocortical tumors

Edoxaban for the Long-Term Therapy of Venous Thromboembolism : Should the Criteria for Dose Reduction be Revised?

Edoxaban is used for venous thromboembolism (VTE) treatment. Real-life data are lacking about its use in long-term therapy. We aimed to assess the efficacy and the safety of edoxaban for long-term VTE treatment in a real-life setting. Patients with VTE included in the egistro nformatizado nfermedad rombombólica (RIETE) registry, receiving edoxaban 60 or 30 mg daily were prospectively followed up to validate the benefit of using different dosages. The main outcome was the composite of VTE recurrences or major bleeding in patients with or without criteria for dose reduction. Multivariable analysis to identify predictors for the composite outcome was performed. From October 2015 to November 2019, 562 patients received edoxaban for long-term therapy. Most (94%) of the 416 patients not meeting criteria for dose reduction received 60 mg daily, and 92 patients meeting criteria (63%) received 30 mg daily. During treatment, two patients developed recurrent VTE, six had major bleeding and nine died (2 from fatal bleeding). Among patients not meeting criteria for dose reduction, those receiving 30 mg daily had a higher rate of the composite event (hazard ratio (HR) 8.37; 95% confidence interval (CI) 1.12-42.4) and a significant higher mortality rate (HR 31.1; 95% CI 4.63-262) than those receiving 60 mg. Among patients meeting criteria for dose reduction, those receiving 60 mg daily had no events, and a nonsignificantly higher mortality rate (HR 5.04; 95% CI 0.54-133) than those receiving 30 mg daily. In conclusion, edoxaban seems to be effective and safe for long-term VTE treatment in real life. Criteria for dose reduction should be reformulated

The anti MRSA biofilm activity of Thymus vulgaris essential oil in nanovesicles

Background: Thymus vulgaris essential oil (T) could be an alternative to classical antibiotics against bacterial biofilms, which show increased tolerance to antibiotics and host defence systems and contribute to the persistence of chronic bacterial infections. Hypothesis: A nanovesicular formulation of T may chemically protect the structure and relative composition of its multiple components, potentially improving its antibacterial and antibiofilm activity. Study design: We prepared and structurally characterized T in two types of nanovesicles: nanoliposomes (L80-T) made of Soybean phosphatidylcholine (SPC) and Polysorbate 80 (P80) [SPC:P80:T 1:0.75:0.3 w:w], and nanoarchaeosomes (A80-T) made of SPC, P80 and total polar archaeolipids (TPA) extracted from archaebacteria Halorubrum tebenquichense [SPC:TPA:P80:T 0.5:0.50.75:0.7 w:w]. We determined the macrophage cytotoxicity and the antibacterial activity against Staphylococcus aureus ATCC 25,923 and four MRSA clinical strains. Results: L80-T (Z potential −4.1 ± 0.6 mV, ∼ 115 nm, ∼ 22 mg/ml T) and A80-T (Z potential −6.6 ± 1.5 mV, ∼ 130 nm, ∼ 42 mg/ml T) were colloidally and chemically stable, maintaining size, PDI, Z potential and T concentration for at least 90 days. While MIC 90 of L80-T was > 4 mg/ml T, MIC 90 of A80-T was 2 mg/ml T for all S. aureus strains. The antibiofilm formation activity was maximal for A80-T, while L80-T did not inhibit biofilm formation compared to untreated control. A80-T significantly decreased the biomass of preformed biofilms of S. aureus ATCC 25,923 strain and of 3 of the 4 clinical MRSA isolates at 4 mg/ml T. It was found that the viability of J774A.1 macrophages was decreased significantly upon 24 h incubation with A80-T, L80-T and T emulsion at 0.4 mg/ml T. These results show that from 0.4 mg/ml T, a value lower than MIC 90 and the one displaying antibiofilm activity, with independence of its formulation, T significantly decreased the macrophages viability. Conclusion: Overall, because of its lower MIC 90 against planktonic bacteria, higher antibiofilm formation capacity and stability during storage, A80-T resulted better antibacterial agent than T emulsion and L80-T. These results open new avenues to explode the A80-T antimicrobial intracellular activity.Fil: Perez, Ana Paula. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; ArgentinaFil: Perez, Noelia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; ArgentinaFil: Suligoy Lozano, Carlos Mauricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Altube, María Julia. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: de Farias, Marcelo Alexandre. No especifíca;Fil: Portugal, Rodrigo Villares. No especifíca;Fil: Buzzola, Fernanda Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Morilla, María José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; ArgentinaFil: Romero, Eder Lilia. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Una exploración de la parentalidad en la Modernidad líquida

While chemical contraception made “sex without reproduction” possible, new reproductive technologies facilitate “reproduction without sex”, which at the same time enables a formidable range of apparently naturalized family configurations, in liquid modernity. We are currently assisting in the construction of links, roles and functions that move away from those traditional paradigms, which until the end of the 20th century seemed immutable. In this research, the aim is to contribute –from a psychoanalytic perspective- to the exploration of those representations of parenting that take place in the context of liquid Modernity, based on the supply –and demand- of medically assisted reproduction. In reference to the research that is currently carried out from the Graduate School of the UNLaM (CyTMA2 2020 Call “New representations of parenting. From assisted reproduction in liquid modernity”), we present below, as the first progress report, its theoretical framework.Mientras la anticoncepción química hizo posible el “sexo sin reproducción”, las nuevas tecnologías reproductivas facilitan la “reproducción sin sexo”, lo que a la vez da lugar, en la Modernidad líquida, a un formidable abanico de configuraciones familiares, aparentemente naturalizadas. Asistimos en la actualidad a la construcción de vínculos, roles y funciones que se alejan de aquellos paradigmas tradicionales, que hasta fines del siglo XX parecían inmutables. En esta pesquisa aspiramos a contribuir –desde una perspectiva psicoanalítica- a la exploración de aquellas representaciones de la parentalidad que tienen lugar en el contexto de la Modernidad líquida, a partir de la oferta –y la demanda- de reproducción médicamente asistida. Presentamos a continuación, en referencia a esta investigación que actualmente se lleva a cabo desde la Escuela de Posgrado de la UNLaM (Convocatoria CyTMA2 2020 “Nuevas representaciones de la parentalidad. A partir de la reproducción asistida en la Modernidad líquida”), un primer informe de avances, que comprende el marco teórico de la misma

8-Amide and 8-carbamate substitution patterns as modulators of 7-hydroxy-4-methylcoumarin's antidepressant profile: Synthesis, biological evaluation and docking studies

Psychiatric and neurological disorders affect millions of people worldwide. Currently available treatments may help to improve symptoms, but they cannot cure the diseases. Therefore, there is an urgent need for potent and safe therapeutic solutions. 8-Amide and 8-carbamatecoumarins were synthetized and evaluated as human monoamine oxidase A and B (hMAO-A and hMAO-B) inhibitors. Comparison between both scaffolds has been established, and we hypothesized that the introduction of different substituents can modulate hMAO activity and selectivity. N-(7-Hydroxy-4-methylcoumarin-8-yl)-4-methylbenzamide (9) and ethyl N-(7-hydroxy-4-methylcoumarin-8-yl)carbamate (20) proved to be the most active and selective hMAO-A inhibitors (IC50 = 15.0 nM and IC50 = 22.0 nM, respectively), being compound 9 an irreversible hMAO-A inhibitor twenty-four times more active in vitro than moclobemide, a drug used in the treatment of depression and anxiety. Based on PAMPA assay results, both compounds proved to be good candidates to cross the blood-brain barrier. In addition, these compounds showed non-significant cytotoxicity on neuronal viability assays. Also, the best compound proved to have a t1/2 of 6.84 min, an intrinsic clearance of 195.63 μL min−1 mg−1 protein, and to be chemically stable at pH 3.0, 7.4 and 10.0. Docking studies were performed to better understand the binding affinities and selectivity profiles for both hMAO isoforms. Finally, theoretical drug-like properties calculations corroborate the potential of both scaffolds on the search for new therapeutic solutions for psychiatric disorders as depressionThis research was funded by Consellería de Cultura, Educación e Ordenación Universitaria (EM2014/016), Ministerio de Ciencia e Innovación (PID2020-116076RJ-I00/AEI/10.13039/501100011033) and Fundação para a Ciência e Tecnologia (PTDC/ASP-PES/28397/2017, CEECIND/02423/2018, UIDB/00081/2020, LA/P/0056/2020 and EXPL/BIA-BQM/0492/2021). Financial support from the Xunta de Galicia (Centro de investigación de Galicia accreditation 2019–2022) and the European Union (European Regional Development Fund - ERDF), is also gratefully acknowledged. M.I.R.-F. acknowledges the economic support from the Spanish Ministry of Science, Innovation and Universities; Spanish Research Agency; and European Regional Development Funds (grant PID2021-122650OB-I00) and from CSIC (PIE-202080E118)S

Fighting HIV/AIDS in a developing country: lessons from a small cohort from the largest Brazilian city

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International multicenter observational study on assessment of ventilatory management during general anaesthesia for robotic surgery and its effects on postoperative pulmonary complication (AVATaR) : study protocol and statistical analysis plan

Introduction: Robotic-assisted surgery (RAS) has emerged as an alternative minimally invasive surgical option. Despite its growing applicability, the frequent need for pneumoperitoneum and Trendelenburg position could significantly affect respiratory mechanics during RAS. AVATaR is an international multicenter observational study aiming to assess the incidence of postoperative pulmonary complications (PPC), to characterise current practices of mechanical ventilation (MV) and to evaluate a possible association between ventilatory parameters and PPC in patients undergoing RAS. Methods and analysis: AVATaR is an observational study of surgical patients undergoing MV for general anaesthesia for RAS. The primary outcome is the incidence of PPC during the first five postoperative days. Secondary outcomes include practice of MV, effect of surgical positioning on MV, effect of MV on clinical outcome and intraoperative complications. Ethics and dissemination: This study was approved by the Institutional Review Board of the Hospital Israelita Albert Einstein. The study results will be published in peer-reviewed journals and disseminated at international conferences. Trial registration number: NCT02989415; Pre-results