Transversalidad de las técnicas de modelado matemático en Farmacia con la ayuda de una hoja de cálculo

The implementation of the EHEA in Pharmacy studies will lead to foster student self-learning. This way the student abilities to apply knowledge, learned in some subjects, to search knowledge in any other will be tested. Among such applicative knowledge, we can consider the mathematical modelling techniques, included in the field of Mathematics. This article draws attention to the usefulness of popular spreadsheets for Pharmacy students interested in the application of mathematical modelling techniques. Roughly speaking, a pharmacy student will probably have to perform mathematical calculations and experimental data visualizations, especially in the practice syllabus of some of his subjects. The use of software is important in this respect, not only in the learning step of the mathematical concepts in the corresponding math subject, but also in its application to other Pharmacy subjects. What application software can be chosen for the students? Although there are many candidates, a spreadsheet offers some capabilities that make it ideal for a Pharmacy student: short learning time, wide availability on different computer platforms and flexibility to carry out a variety of computational tasks. Finally, we present a Web page which provides self-learning material to Pharmacy students for harnessing the potential offered by the spreadsheets Excel (Microsoft Office) and Calc (OpenOffice.org) in the study of their subjects in Pharmacy.La implantación del EEES en las titulaciones en Farmacia va a significar la potenciación del autoaprendizaje por parte del alumno. Esto va a poner a prueba la capacidad de aplicar conocimientos adquiridos en unas materias, para entender y conocer otras. Entre dichos conocimientos, se encuentran las técnicas de modelado matemático, incluidas en el campo de las Matemáticas. El presente artículo reflexiona acerca de la utilidad de las populares hojas de cálculo como software dirigido al alumno. Un alumno de Farmacia, probablemente, tendrá que realizar cálculos matemáticos y representaciones gráficas con datos experimentales, muy especialmente en las prácticas de algunas de sus asignaturas. La utilización de un software es, en este sentido, especialmente importante, no sólo en la fase de aprendizaje de dichos conocimientos matemáticos en la correspondiente asignatura del título, sino a la hora de disponer de una herramienta que facilite su aplicación en otras. ¿Qué software podemos elegir para el alumno? A pesar de que existen multitud de candidatos, una hoja de cálculo reúne una serie de características que la hacen idónea para un alumno de Farmacia: corto tiempo de aprendizaje, amplia disponibilidad en distintas plataformas y flexibilidad para poder realizar una gran diversidad de tareas, entre otras propiedades. Finalmente, como ejemplo se presenta una página Web, http://www.ugr.es/~focana/farmaspreadsheet.htm, que facilita material para ayudar al alumno de Farmacia a aprovechar las posibilidades que ofrecen las hojas de cálculo Excel (Microsoft Office) y Calc (OpenOffice.org) en el estudio de sus asignaturas en Farmacia

Targeting fatty acid-binding protein 4 improves pathologic features of aortic stenosis

Aortic stenosis (AS) is a fibrocalcific disease of the aortic valves (AVs). Sex-differences in AS pathophysiology have recently been described. High levels of fatty acid-binding protein 4 (FAPB4) in atherosclerotic plaques have been associated with increased local inflammation, endothelial dysfunction, and plaque vulnerability. FABP4 pharmacological blockade has been shown to be effective for the treatment of atherosclerosis by modulating metabolic and inflammatory pathways. We aimed to analyze the sex-specific expression of FABP4 in AS and its potential role as a therapeutic target. A total of 226 patients (61.5% men) with severe AS undergoing surgical AV replacement were recruited. The FABP4 levels were increased in the AVs of AS patients compared to the control subjects, showing greater expression in the fibrocalcific regions. Male AVs exhibited higher levels of FABP4 compared to females, correlating with markers of inflammation (IL-6, Rantes), apoptosis (Bax, caspase-3, Bcl-2), and calcification (IL-8, BMP-2 and BMP-4). VICs derived from AS patients showed the basal expression of FABP4 in vitro. Osteogenic media induced upregulation of intracellular and secreted FABP4 levels in male VICs after 7 days, along with increased levels of inflammatory, pro-apoptotic, and osteogenic markers. Treatment with BMS309403, a specific inhibitor of FABP4, prevented from all of these changes. Thus, we propose FABP4 as a new sex-specific pharmacological therapeutic target in AS.This research was funded by Miguel Servet contract CP13/00221 from the Instituto de Salud Carlos III-FEDER, Fondo de Investigaciones Sanitarias [PI18/01875; PI21/00280]. M.G. is supported by a Miguel Servet Foundation PhD studentship, E.M.-N. is supported by a Margarita Salas postdoctoral fellowship (ULL-MS-P14), L.M. is supported by a PFIS (FI19/00302) PhD studentship, E.J. (CD19/00251) is supported by a Sara Borrell postdoctoral fellowship

Characterization of the sex-specific pattern of angiogenesis and lymphangiogenesis in aortic stenosis

Objective: We aim to analyze sex-related dierences in angiogenesis and lymphangiogenesis in aortic valves (AVs) and valve interstitial cells (VICs) from aortic stenosis (AS) patients. Approach and Results: Totally 230 patients (59% men) with severe AS undergoing surgical valve replacement were recruited. The density of total neovessels was higher in AVs from men as compared to women. Both small and medium neovessels were more abundant in men’s AVs. Accordingly, male AVs exhibited higher CD31 and VE-cadherin expressions. The levels of the pro-angiogenic markers, such as vascular endothelial growth factor (VEGF)-A, VEGF receptor (VEGFR)1, VEGFR2, insulin-like growth factor-binding protein-2 (IGFBP-2), interleukin (IL)-8, chemerin, and fibroblast growth factor (FGF)-7, were increased in AVs from men. Transforming growth factor-β expression was higher in male AVs. The expression of antiangiogenic molecules thrombospondin (Tsp)-1, endostatin, and CD36 was upregulated in male AVs, although the levels of Tsp-2, IL-4, IL-12p70, and chondromodulin-1 were similar between both sexes. The number of lymphatic vessels and the expression of the lymphangiogenic markers Lyve-1 and D2-40 was higher in men’s AV as well as VEGF-C, VEGF-D, and VEGFR3. Multivariate analyses adjusted for confounders further validated the sex-dependent expression of these targets. VICs isolated from men’s AVs secreted higher amounts of the pro-angiogenic factors, VEGF-A, VEGFR1, IGFBP-2, and FGF-7, as well as the pro-lymphangiogenic factors, VEGF-C, VEGF-D, and VEGFR3, than women without changes in antiangiogenic markers. Conclusion: Our data show that aberrant angiogenic and lymphangiogenic cues are over-represented in male AVs. Importantly, the VIC is a relevant source of multiple morphogens involved in angiogenesis and lymphangiogenesis likely endowing the AV of men with the predominant calcific AS phenotypes.This work was supported by a Miguel Servet contract (CP13/00221) and by Fondo de Investigaciones Sanitarias (PI18/01875; PI21/00280) from the Instituto de Salud Carlos III - FEDER. LM was supported by a PFIS Ph.D. studentship (FI19/00302). EJ was supported by a Sara Borrell postdoctoral fellowship (CD19/00251). EM-N was supported by a Margarita Salas postdoctoral fellowship (ULL-MS-P14). MG was supported by a Miguel Servet Foundation Ph.D. studentship

Sex-dependent expression of neutrophil gelatinase-associated lipocalin in aortic stenosis

Background: Accumulating evidence suggest the existence of sex-related differences in the pathogenesis of aortic stenosis (AS) with inflammation, oxidative stress, fibrosis and calcification being over-represented in men. Neutrophil gelatinase-associated lipocalin (NGAL) is expressed in a myriad of tissues and cell types, and it is associated with acute and chronic pathological processes comprising inflammation, fibrosis or calcification. Sex-dependent signatures have been evidenced for NGAL which expression has been associated predominantly in males to metabolic and cardiovascular disorders. We aimed to analyse sex-related differences of NGAL in AS and its role in the inflammatory and fibrocalcific progression of AS. Methods and results: 220 (60.45% men) patients with severe AS elective for surgical aortic valve (AV) replacement were recruited. Immunohistochemistry revealed higher expression of NGAL in calcific areas of AVs and that was validated by qPCR in in 65 (60% men) donors. Valve interstitial cells (VICs) were a source of NGAL in these samples. Proteome profiler analyses evidenced higher expression of NGAL in men compared to women, and that was further validated by ELISA. NGAL expression in the AV was correlated with inflammation, oxidative stress, and osteogenic markers, as well as calcium score. The expression of NGAL, both intracellular and secreted (sNGAL), was significantly deregulated only in calcifying male-derived VICs. Depletion of intracellular NGAL in calcifying male-derived VICs was associated with pro-inflammatory profiles, dysbalanced matrix remodelling and pro-osteogenic profiles. Conversely, exogenous NGAL mediated inflammatory and dysbalanced matrix remodelling in calcifying VICs, and all that was prevented by the pharmacological blockade of NGAL. Conclusions: Owing to the over-expression of NGAL, the AV from men may be endowed with higher expression of inflammatory, oxidative stress, matrix remodelling and osteogenic markers supporting the progression of calcific AS phenotypes. The expression of NGAL in the VIC emerges as a potential therapeutic checkpoint, with its effects being potentially reverted by the pharmacological blockade of extracellular NGAL.This research was funded by Miguel Servet contract CP13/00221 from Instituto de Salud Carlos III-FEDER, Fondo de Investigaciones Sanitarias [PI18/01875; PI21/00280]. M.G. is supported by a Miguel Servet Foundation PhD studentship, E.M.-N is supported by a Margarita Salas postdoctoral fellowship (ULL-MS-P14), L.M. is supported by a PFIS (FI19/00302) PhD studentship, E.J. (CD19/00251) is supported by a Sara Borrell postdoctoral fellowship

Estrogen Receptor-Alpha (ESR1) Governs the Lower Female Reproductive Tract Vulnerability to Candida albicans

Estradiol-based therapies predispose women to vaginal infections. Moreover, it has long been known that neutrophils are absent from the vaginal lumen during the ovulatory phase (high estradiol). However, the mechanisms that regulate neutrophil influx to the vagina remain unknown. We investigated the neutrophil transepithelial migration (TEM) into the vaginal lumen. We revealed that estradiol reduces the CD44 and CD47 epithelial expression in the vaginal ectocervix and fornix, which retain neutrophils at the apical epithelium through the estradiol receptor-alpha. In contrast, luteal progesterone increases epithelial expression of CD44 and CD47 to promote neutrophil migration into the vaginal lumen and Candida albicans destruction. Distinctive to vaginal mucosa, neutrophil infiltration is contingent to sex hormones to prevent sperm from neutrophil attack; although it may compromise immunity during ovulation. Thus, sex hormones orchestrate tolerance and immunity in the vaginal lumen by regulating neutrophil TEM.The authors thank the units of flow cytometry, cell culture and statistical analysis. We are grateful to J. Villarejo, M. Fernandez-Garcia, and F. Sanchez-Cobos, for expert help and support. This work was partially supported by Fundacion Mutua Madrilena and the Ministry of Economy and Competitiveness ISCIII-FIS grants PI13/00269, PI16/00050, and PI17/01324, co-financed by ERDF (FEDER) Funds from the European Commission, ``A way of making Europe.´´ MR holds a Miguel Servet II contract (CPII14/00009). LS-M holds a IiSGM intramural contract.S

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

Beneficial Effects of Mineralocorticoid Receptor Pathway Blockade against Endothelial Inflammation Induced by SARS-CoV-2 Spike Protein

Background: Vascular endothelial cells activation and dysfunction mediate inflammation and abnormal coagulation in COVID-19 patients. Mineralocorticoid receptor (MR) signaling and its downstream target Galectin-3 (Gal-3) are known to mediate cardiovascular inflammation and might be involved in the pathogenesis of COVID-19 complications. Accordingly, we aimed to investigate the potential beneficial effects of MR antagonism and Gal-3 inhibition on the inflammatory response induced by SARS-CoV-2 Spike protein in human aortic endothelial cells (HAECs). Methods: HAECs were treated with recombinant SARS-COV2 Spike (S) protein. MR antagonists (namely spironolactone and eplerenone) or the Gal-3 inhibitor G3P-01 were supplemented before and after S protein challenge. HAECs supernatants were assessed by ELISA or Western blotting. Results: HAECs treated with recombinant S protein resulted in enhanced secretion of inflammatory molecules (interleukin-6, monocyte chemoattractant protein-1, interleukin-18, interleukin-27, and interferon-γ) as well as in the thrombosis marker plasminogen activator inhibitor (PAI)-1. This was prevented and reversed by both MR antagonists and G3P-01. Conclusions: These findings indicate that MR/Gal-3 pathway blockade could be a promising option to reduce endothelial inflammation in SARS-CoV-2 infection