Integrated Surface-Groundwater Modelling of Nitrate Concentration in Mediterranean Rivers, the Júcar River Basin District, Spain

[EN] High nutrient discharge from groundwater (GW) into surface water (SW) have multiple undesirable effects on river water quality. With the aim to estimate the impact of anthropic pressures and river-aquifer interactions on nitrate status in SW, this study integrates two hydrological simulation and water quality models. PATRICAL models SW-GW interactions and RREA models streamflow changes due to human activity. The models were applied to the Jucar River Basin District (RBD), where 33% of the aquifers have a concentration above 50 mg NO3-/L. As a result, there is a direct linear correlation between the nitrate concentration in rivers and aquifers (Jucar r(2) = 0.9, and Turia r(2) = 0.8), since in these Mediterranean basins, the main amount of river flows comes from groundwater discharge. The concentration of nitrates in rivers and GW tends to increase downstream of the district, where artificial surfaces and agriculture are concentrated. The total NO3- load to Jucar RBD rivers was estimated at 10,202 tN/year (239 kg/km(2)/year), from which 99% is generated by diffuse pollution, and 3378 tN/year (79 kg/km(2)/year) is discharged into the Mediterranean Sea. Changes in nitrate concentration in the RBD rivers are strongly related to the source of irrigation water, river-aquifer interactions, and flow regulation. The models used in this paper allow the identification of pollution sources, the forecasting of nitrate concentration in surface and groundwater, and the evaluation of the efficiency of measures to prevent water degradation, among other applications.The first author's research is partially funded by a PhD scholarship from the food research stream of the program "Colombia Cientifica-Pasaporte a la Ciencia", granted by the Colombian Institute for Educational Technical Studies Abroad (Instituto Colombiano de Credito Educativo y Estudios Tecnicos en el Exterior, ICETEX). The authors thank the Spanish Research Agency (AEI) for the financial support to RESPHIRA project (PID2019-106322RB-100)/AEI/10.13039/501100011033.Dorado-Guerra, DY.; Paredes Arquiola, J.; Pérez-Martín, MÁ.; Tafur Hermann, H. (2021). Integrated Surface-Groundwater Modelling of Nitrate Concentration in Mediterranean Rivers, the Júcar River Basin District, Spain. Sustainability. 13(22):1-21. https://doi.org/10.3390/su132212835S121132

JKST6, a novel multikinase modulator of the BCR-ABL1/STAT5 signaling pathway that potentiates direct BCR-ABL1 inhibition and overcomes imatinib resistance in chronic myelogenous leukemia

Chronic myelogenous leukemia (CML) is a hematological malignancy that highly depends on the BCR-ABL1/STAT5 signaling pathway for cell survival. First-line treatments for CML consist of tyrosine kinase inhibitors that efficiently target BCR-ABL1 activity. However, drug resistance and intolerance are still therapeutic limitations in Ph+ cells. Therefore, the development of new anti-CML drugs that exhibit alternative mechanisms to overcome these limitations is a desirable goal. In this work, the antitumoral activity of JKST6, a naphthoquinone-pyrone hybrid, was assessed in imatinib-sensitive and imatinib-resistant human CML cells. Live-cell imaging analysis revealed JKST6 potent antiproliferative activity in 2D and 3D CML cultures. JKST6 provoked cell increase in the subG1 phase along with a reduction in the G0/G1 phase and altered the expression of key proteins involved in the control of mitosis and DNA damage. Rapid increases in Annexin V staining and activation/cleavage of caspases 8, 9 and 3 were observed after JKST6 treatment in CML cells. Of interest, JKST6 inhibited BCR-ABL1/STAT5 signaling through oncokinase downregulation that was preceded by rapid polyubiquitination. In addition, JKST6 caused a transient increase in JNK and AKT phosphorylation, whereas the phosphorylation of P38-MAPK and Src was reduced. Combinatory treatment unveiled synergistic effects between imatinib and JKST6. Notably, JKST6 maintained its antitumor efficacy in BCR-ABL1-T315I-positive cells and CML cells that overexpress BCR-ABL and even restored imatinib efficacy after a short exposure time. These findings, together with the observed low toxicity of JKST6, reveal a novel multikinase modulator that might overcome the limitations of BCR-ABL1 inhibitors in CML therapy.This research has been funded by Spanish Ministry of Economy and Competitiveness - MINECO - (SAF 2015–65113-C2–1-R and RTI2018–094356-B-C21 to AEB, SAF2015–65113-C2–2 to LFP, SAF2017–88026-R to JL) with the co-funding of European Regional Development Fund (EU-ERDF), Canary Islands Government (CEI2018–23/ACIISI to BG, CEI2019–08/ACIISI to BG and LFP, ProID2021010037 to AEB, LFP and BG) and "Juan de la Cierva Incorporacion" Grant Program from the Ministry of Science, Innovation and Universities (IJC2018-035193-I to CR). This project has been also supported by Alfredo Martin-Reyes Foundation (Arehucas)-Canary Islands Foundation for Cancer Research (FICIC). HAT is recipient of a predoctoral program grant from ULPGC (2016). JCM was funded by the Instituto de Salud Carlos III through a Miguel Servet program (CPII17/ 00015)

Definite and indeterminate nonalcoholic steatohepatitis share similar clinical features and prognosis: A longitudinal study of 1893 biopsy-proven nonalcoholic fatty liver disease subjects

[Background and Aim] Histological score systems may not fully capture the essential nonalcoholic steatohepatitis (NASH) features, which is one of the leading causes of screening failure in clinical trials. We assessed the NASH distribution and its components across the fibrosis stages and their impact on the prognosis and their relationship with the concept of metabolic-associated fatty liver disease (MAFLD).[Methods] Spanish multicenter study including 1893 biopsy-proven nonalcoholic fatty liver disease (NAFLD) patients from HEPAmet registry. NASH was diagnosed by NAS score ≥4 (including steatosis, ballooning and lobular inflammation) and fibrosis by Kleiner score. The presence of MAFLD was determined. Progression to cirrhosis, first episode of decompensated cirrhosis and death were collected during the follow-up (4.7 ± 3.8 years).[Results] Fibrosis was F0 34.3% (649/1893), F1 27% (511/1893), F2 16.5% (312/1893), F3 15% (284/1893) and F4 7.2% (137/1893). NASH diagnosis 51.9% (982/1893), and its individual components (severe steatosis, ballooning and lobular inflammation), increased from F0 (33.6%) to F2 (68.6%), and decreased significantly in F4 patients (51.8%) (P = .0001). More than 70% of non-NASH patients showed some inflammatory activity (ballooning or lobular inflammation), showing a similar MAFLD rate than NASH (96.2% [945/982] vs. 95.2% [535/562]) and significantly higher than nonalcoholic fatty liver (NAFL) subjects (89.1% [311/349]) (P < .0001). Progression to cirrhosis was similar between NASH (9.5% [51/539]) and indeterminate NASH (7.9% [25/316]), and higher than steatosis (5% [14/263]) (logRank 8.417; P = .015). Death and decompensated cirrhosis were similar between these.[Conclusions] The prevalence of steatohepatitis decreased in advanced liver disease. However, most of these patients showed some inflammatory activity histologically and had metabolic disturbances. These findings should be considered in clinical trials whose main aim is to prevent cirrhosis progression and complications, liver transplant and death.This project has been partially funded by the ‘Consejería de Salud de la Junta de Andalucía’ (PI-0075-2014) and the ‘Spanish Ministry of Economy, Innovation and Competition, Instituto de Salud Carlos III’ (PI19/01404, PI16/01842, PI17/00535 and GLD19/00100).Peer reviewe

Estrategias de uso racional de medicamentos en personas mayores como mejora de la calidad de vida y de promoción del bienestar

El proyecto “Estrategias de uso racional de medicamentos en personas mayores como mejora de la calidad de vida y de promoción del bienestar” se basa en la elaboración y diseño de estrategias de prevención y mejora en torno al cumplimiento terapéutico, el uso racional del medicamento, y la identificación temprana de reacciones adversas a medicamentos, entre otros problemas relacionados con el medicamento. Este proyecto es una continuación del anterior ApS UCM 2019 “Identificación de problemas relacionados con el medicamento y estrategias de mejora en personas mayores”. En esta ocasión, y por la pandemia por COVID-19, este ApS será virtual, desarrollándose diversos talleres en formato de vídeo para dar formación a las personas mayores en materia de medicamento y que se centrarán en el tratamiento de las distintas patologías de la meta 3.4. de los ODS 2030, con el fin de aumentar la calidad de vida y el bienestar social de este colectivo. Esta actividad se integra en la docencia de las asignaturas de Farmacología General, y Farmacología y Farmacoterapia del Grado en Farmacia y del Doble Grado de Farmacia y Nutrición como estrategia de aprendizaje para consolidar y profundizar lo aprendido en estas materias

Relationship between IGF-1 and body weight in inflammatory bowel diseases: Cellular and molecular mechanisms involved

Inflammatory bowel diseases (IBD), represented by ulcerative colitis (UC) and Crohn''s disease (CD), are characterized by chronic inflammation of the gastrointestinal tract, what leads to diarrhea, malnutrition, and weight loss. Depression of the growth hormone-insulin-like growth factor-1 axis (GH-IGF-1 axis) could be responsible of these symptoms. We demonstrate that long-term treatment (54 weeks) of adult CD patients with adalimumab (ADA) results in a decrease in serum IGF-1 without changes in serum IGF-1 binding protein (IGF1BP4). These results prompted us to conduct a preclinical study to test the efficiency of IGF-1 in the medication for experimental colitis. IGF-1 treatment of rats with DSS-induced colitis has a beneficial effect on the following circulating biochemical parameters: glucose, albumin, and total protein levels. In this experimental group we also observed healthy maintenance of colon size, body weight, and lean mass in comparison with the DSS-only group. Histological analysis revealed restoration of the mucosal barrier with the IGF-1 treatment, which was characterized by healthy quantities of mucin production, structural maintenance of adherers junctions (AJs), recuperation of E-cadherin and ß-catenin levels and decrease in infiltrating immune cells and in metalloproteinase-2 levels. The experimentally induced colitis caused activation of apoptosis markers, including cleaved caspase 3, caspase 8, and PARP and decreases cell-cycle checkpoint activators including phosphorylated Rb, cyclin E, and E2F1. The IGF-1 treatment inhibited cyclin E depletion and partially protects PARP levels. The beneficial effects of IGF-1 in experimental colitis could be explained by a re-sensitization of the IGF-1/IRS-1/AKT cascade to exogenous IGF-1. Given these results, we postulate that IGF-1 treatment of IBD patients could prove to be successful in reducing disease pathology. © 2021 The Author

Pharmacist role in the nutrition area at the European level

Una vez licenciado, el farmacéutico puede optar por un elevado número de salidas profesionales, tanto en el sector público al servicio de los diferentes cuerpos y administraciones, como en el sector privado. Los perfiles profesionales más frecuentes del farmacéutico pueden englobarse en 4 modalidades: Oficina de Farmacia (Farmacia Comunitaria), Farmacia Hospitalaria, Distribución e Industria Farmacéutica o Análisis y Salud Pública. A nivel de oficina de farmacia, el farmacéutico, junto a la dispensación de medicamentos, ejerce un destacado papel como asesor y consejero de salud. Las estadísticas desvelan que una de cada cuatro personas que entran en una farmacia no adquiere medicamentos, sino que sólo pide un consejo sanitario, incluyendo asesoría sobre dietas, alimentación y nutrición. Además, la aparición en los últimos años de complementos alimenticios, de venta en farmacia, hace que el farmacéutico deba formarse y comportarse como profesional en lo que respecta a temas de nutrición. Otra salida profesional, como la inspección Farmacéutica, incluye la supervisión de agua y alimentos no animales, por lo que el farmacéutico debe tener un amplio conocimiento sobre la legislación, sanidad y análisis de alimentos. Por otro lado, la industria farmacéutica incluye una amplia variedad de salidas profesionales, incluyéndose dirección técnica, control de calidad y de fabricación, gestión comercial, documentación científica o análisis. La industria agroalimentaria ha experimentado importantes cambios en las últimas décadas, exigiendo profesionales en la materia, como dietistas o analistas bromatológicos, dentro de un equipo multidisciplinar. En este sentido, el farmacéutico, a través del nuevo grado en Farmacia, debe adquirir una base sólida en el campo de la nutrición y bromatología. Así, las competencias recogidas en la Orden CIN/2137/2008 ponen de manifiesto la importancia de la formación del futuro farmacéutico en el ámbito de la alimentación.Once graduated, the pharmacist can choose a high number of professional skills, both in public and private sectors. The most frequent professional skills of the pharmacist can be included in 4 different fields: Pharmacy Office (Communitary Pharmacy), Hospital Pharmacy, Distribution and Pharmaceutical Industry or Analysis and Public Health. At the pharmacy office level, the pharmacist, along with the medicines dispensation, exercises an out-standing role as health adviser. The statistics reveal that 25% of the pharmacy customers do not acquire medicines, but they only ask for a sanitary advice, including nutrition and dietetic consultations. Moreover, in the last years nutritive supplements have been included within the pharmaceutical sales. Thus, the pharmacist should be formed about nutritional topics. Another professional skill, like the pharmaceutical inspection, includes drinkable water and non-animal foodstuffs analyses. Then, the pharmacist should have a wide knowledge on legislation, health and food analysis. On the other hand, the pharmaceutical industry includes a wide variety of professional skills, including technical direction, quality control, commercial management, scientific documentation or analysis. Finally, the agro-alimentary industry has experienced important changes in the last decades, demanding professionals in the matter, like dietitians or food analysts. In this sense, the pharmacist, across the new degree in Pharmacy, must acquire a solid base in the nutrition and bromatology field. Therefore, the competences gathered in the Disposition CIN / 2137/2008 reveals the importance of the formation of the future pharmacist in the nutrition area

The new degree in pharmacy. Is it enough for the formative needs in the nutrition area?

La importancia de la alimentación en la consecución de la salud y en la prevención de la enfermedad y la necesidad de un buen control de la dieta para alcanzar resultados satisfactorios en la reducción del riesgo, tratamiento y control de muchas de las enfermedades crónicas, es un hecho documentado científicamente y de gran relevancia en la sociedad actual. La Orden CIN/2137/2008, de 3 de julio establece los requisitos para la verificación de los títulos universitarios oficiales que habiliten para el ejercicio de la profesión farmacéutica, abarcando diversas competencias que aluden directamente a la formación del farmacéutico en el campo de la nutrición. Entre ellas se incluyen 1) Prestar consejo terapéutico en farmacoterapia y dietoterapia, así como consejo nutricional y alimentario a los usuarios de los establecimientos en los que presten servicio. 2) Conocer la relación existente entre la alimentación y salud, y la importancia de la dieta en el tratamiento y prevención de las enfermedades. 3) Desarrollar análisis higiénico-sanitarios (bioquímico, bromatológico, microbiológicos, parasitológicos) relacionados con la salud en general y con los alimentos y medio ambiente en particular. 4) Conocer las técnicas analíticas relacionadas con el diagnóstico de laboratorio de tóxicos, alimentos y medioambiente. En este sentido, el nuevo Grado en Farmacia aprobado por el Consejo de Gobierno de la Universidad de Granada incluye la asignatura troncal “Nutrición y Bromatología” de 6 créditos. Sin embargo los créditos obligatorios aprobados por la ANECA para esta materia en 8 Universidades Españolas oscilan entre 7,5 para Sevilla y 12 créditos para Madrid con una media de 9,4 créditos. De esta forma ¿Es posible cubrir con los 6 créditos asignados a esta materia una formación mínima para que el farmacéutico pueda realizar adecuadamente las competencias que se le han asignado?The importance of nutrition on human health and on illness prevention, and the need for a good control of the diet to reach satisfactory results in the reduction of the risk, treatment and control of many of the chronic diseases, is a scientifically documented fact quite relevant in the current society. The Disposition CIN

Association Between Preexisting Versus Newly Identified Atrial Fibrillation and Outcomes of Patients With Acute Pulmonary Embolism

Background Atrial fibrillation (AF) may exist before or occur early in the course of pulmonary embolism (PE). We determined the PE outcomes based on the presence and timing of AF. Methods and Results Using the data from a multicenter PE registry, we identified 3 groups: (1) those with preexisting AF, (2) patients with new AF within 2 days from acute PE (incident AF), and (3) patients without AF. We assessed the 90-day and 1-year risk of mortality and stroke in patients with AF, compared with those without AF (reference group). Among 16 497 patients with PE, 792 had preexisting AF. These patients had increased odds of 90-day all-cause (odds ratio [OR], 2.81; 95% CI, 2.33-3.38) and PE-related mortality (OR, 2.38; 95% CI, 1.37-4.14) and increased 1-year hazard for ischemic stroke (hazard ratio, 5.48; 95% CI, 3.10-9.69) compared with those without AF. After multivariable adjustment, preexisting AF was associated with significantly increased odds of all-cause mortality (OR, 1.91; 95% CI, 1.57-2.32) but not PE-related mortality (OR, 1.50; 95% CI, 0.85-2.66). Among 16 497 patients with PE, 445 developed new incident AF within 2 days of acute PE. Incident AF was associated with increased odds of 90-day all-cause (OR, 2.28; 95% CI, 1.75-2.97) and PE-related (OR, 3.64; 95% CI, 2.01-6.59) mortality but not stroke. Findings were similar in multivariable analyses. Conclusions In patients with acute symptomatic PE, both preexisting AF and incident AF predict adverse clinical outcomes. The type of adverse outcomes may differ depending on the timing of AF onset.info:eu-repo/semantics/publishedVersio

EducaFarma 11.0

Memoria ID2022-036. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2022-2023

Analysis of ancestral and functionally relevant CD5 variants in systemic lupus erythematosus patients

OBJECTIVE: CD5 plays a crucial role in autoimmunity and is a well-established genetic risk factor of developing RA. Recently, evidence of positive selection has been provided for the CD5 Pro224-Val471 haplotype in East Asian populations. The aim of the present work was to further analyze the functional relevance of non-synonymous CD5 polymorphisms conforming the ancestral and the newly derived haplotypes (Pro224-Ala471 and Pro224-Val471, respectively) as well as to investigate the potential role of CD5 on the development of SLE and/or SLE nephritis. METHODS: The CD5 SNPs rs2241002 (C/T; Pro224Leu) and rs2229177 (C/T; Ala471Val) were genotyped using TaqMan allelic discrimination assays in a total of 1,324 controls and 681 SLE patients of Spanish origin. In vitro analysis of CD3-mediated T cell proliferative and cytokine response profiles of healthy volunteers homozygous for the above mentioned CD5 haplotypes were also analyzed. RESULTS: T-cell proliferation and cytokine release were significantly increased showing a bias towards to a Th2 profile after CD3 cross-linking of peripheral mononuclear cells from healthy individuals homozygous for the ancestral Pro224-Ala471 (CC) haplotype, compared to the more recently derived Pro224-Val471 (CT). The same allelic combination was statistically associated with Lupus nephritis. CONCLUSION: The ancestral Ala471 CD5 allele confers lymphocyte hyper-responsiveness to TCR/CD3 cross-linking and is associated with nephritis in SLE patients