[Incorporation of patient-reported outcomes into pharmacy and dermatology departments, in psoriasis and atopic dermatitis patients, as a tool to improve the healthcare quality and health outcomes]. / Incorporación de resultados informados por pacientes con psoriasis y dermatitis atópica en las consultas de atención farmacéutica y dermatología: herramienta que mejora la calidad asistencial y resultados en salud.

INTRODUCTION: Patient-reported outcomes (PROs) provide subjective information about their disease, treatment, and quality of life. OBJECTIVE: To introduce a new system of work coordinated between pharmacists and dermatologists, based on the collection and analysis of PROs to assess its clinical impact as well as patients satisfaction. METHOD: A prospective single-centre observational study was conducted under clinical conditions and included adult patients diagnosed with psoriasis (PS) and atopic dermatitis (AD) between April-2021 and February-2022. Pharmacists and dermatologists agreed on this systematic work. A REDCap® database was designed to facilitate data collection and the subsequent analysis. RESULTS: A total of 288 and 41 patients with PS and AD, respectively, were included. Those who started treatment showed significant improvement with a decrease in PROs and clinical parameters (p < 0.001). The pharmacist made 168 and 7 recommendations to dermatologists for PS and AD patients, respectively, of which 66.07% and 57.1% were accepted. The most common recommendations were «consult with rheumatologist¼ (20.83%), «extend drug regimen¼ (19.64%) and «consider change in treatment¼ (11.90%). Adverse events were reported in 55 and 17 patients with PS and AD, respectively. Of 103 patients, 75% were «very satisfied¼ and 20% «satisfied¼ with the system. CONCLUSIONS: This new working system helps to evaluate the short and long-term effectiveness of treatments and also to identify adverse events, alarm symptoms and co-morbidities in order to optimize therapies. Collaboration between pharmacists and dermatologists reduces decision-making time and patients appreciate better clinical care leading to higher patient satisfaction.

Evaluation of the registry DIALYREG for the assessment of continuous renal replacement techniques in the critically ill patient.

Continuous renal replacement techniques (CRRT) can induce complications and monitoring is crucial to ensure patient safety. We designed a prospective multicenter observational and descriptive study using the DIALYREG registry, an online database located on a REDCap web-based platform that allows real-time data analysis. Our main objective was to identify CRRT-related complications in our intensive care units (ICUs) and implement security measures accordingly. From January 2019 to December 2020, we included 323 patients with admission diagnoses of medical illness (54%), sepsis (24%), postoperative care (20%), and trauma (2%). CRRT indications were homeostasis (42%), oliguria (26%), fluid overload (15%), and hemodynamic optimization (13%). The median initial therapy dose was 30 ml/kg/h (IQR 25-40), and dynamic adjustment was performed in 61% of the treatments. Sets were anticoagulated with heparin (40%), citrate (38%) or no anticoagulation (22%). Citrate anticoagulation had several advantages: more frequent dynamic CRRT dose adjustment (77% vs. 58% with heparin and 56% without anticoagulation, p < 0.05), longer duration of set (median of 55 h, IQR 24-72 vs. 23 h, IQR 12-48 with heparin and 12 h, IQR 12-31 without anticoagulation, p < 0.05), less clotting of the set (26% vs. 46.7% with heparin, p < 0.05), and lower incidence of hypophosphatemia (1% citrate vs. 6% with heparin and 5% without anticoagulation). It was also safe and effective in subgroup analysis of patients with liver disease or sepsis. The main global complications were hypothermia (16%), hypophosphatemia (13%) and metabolic acidosis (10%). Weaning of the therapy was achieved through early discontinuation (56%), nocturnal therapy transition (26%) and progressive SLED (18%). 52% of the patients were discharged from the hospital, while 43% died in the ICU and 5% died during hospitalization. We can conclude that the DIALYREG registry is a feasible tool for real-time control of CRRT in our ICU.

Incidencia de cardiopatía isquémica en el estudio HERMEX y su asociación con los factores de riesgo cardiovascular clásicos / Incidence of ischemic heart disease in the HERMEX study and its association with classical cardiovascular risk factors

Objetivos: El conocimiento sobre la incidencia de enfermedad coronaria en nuestro país es escaso y sus fuentes poco comparables. Fue nuestro objetivo determinar la incidencia de cardiopatía isquémica en una cohorte poblacional con un seguimiento de 7 años y el riesgo asociado a los factores de riesgo cardiovascular clásicos. Métodos: Estudio de cohortes prospectivo en una muestra poblacional de 2833 sujetos, seleccionada por método aleatorio simple entre ciudadanos de 25 a 79 años del Área de Salud Don Benito – Villanueva de la Serena (Badajoz), tasa de respuesta 80,5%. Se recogieron todos los episodios de angina de pecho, infarto de miocardio letal y no letal en individuos sin antecedentes previos de enfermedad cardiovascular. Se calcularon las incidencias acumuladas y las tasas de incidencia ajustadas por 100.000 personas-año por sexo y global. Resultados: De los 2833 participantes iniciales, se excluyeron 103 por antecedentes de enfermedad cardiovascular y 61 por pérdidas, completando el seguimiento 2669 (94,2%). La mediana de seguimiento fue de 6,9 años (RI 6,5 - 7,5), 56,4% mujeres; se registraron 59 eventos. La tasa de incidencia global de cardiopatía isquémica fue 327 casos/100.000 personas-año correspondiendo 470 casos/100.000 al sexo masculino y 211 casos/100.000 personas-año al femenino. Los factores de riesgo cardiovascular clásicos que se asociaron con mayor riesgo de presentar eventos en el seguimiento fueron la dislipemia y la HTA, además del sexo masculino y la edad. Conclusiones: La incidencia de cardiopatía isquémica en la población urbano-rural de Extremadura, es elevada. Los factores de riesgo cardiovascular clásicos más fuertemente asociados a su aparición fueron la dislipemia, y la hipertensión arterial (AU)

Objectives: Knowledge about the incidence of coronary heart disease in our country is scarce and its sources are not comparable. Our aim was to determine the incidence of ischemic heart disease in a population cohort in a 7 years of follow-up, as well as the risk associated with the different classical cardiovascular risk factors. Methods: Cohort study with a population sample of 2833 subjects, selected by the simple random method in a population between 25 and 79, from the Don Benito – Villanueva de la Serena (Badajoz) health area, response rate was 80.5%. All episodes of angina pectoris, lethal and non-lethal myocardial infarction were collected in individuals with no previous history of cardiovascular disease. Cumulative incidences and incidence rates adjusted per 100,000 person-years by sex and overall were calculated. Results: From 2833 initial cohort participants, 103 were excluded due to a history of cardiovascular disease and 61 for losses, 2669 completed the follow-up (94.2%). The median follow-up was 6.9 years (IR 6.5–7.5), 56.4% women; 59 events were recorded. The overall incidence rate of ischemic heart disease was 327 cases/100,000 person-years, corresponding to 470 cases/100,000 for men and 211 cases/100,000 people-years for women. The classical cardiovascular risk factors that were associated with a higher risk of presenting events in the follow-up were dyslipidemia and arterial hypertension, in addition to male sex and age. Conclusions: The incidence of ischemic heart disease in the urban–rural population of Extremadura is high. The classical cardiovascular risk factors most strongly associated with events were dyslipidemia, and arterial hypertension (AU)

[Incidence of ischemic heart disease in the HERMEX study and its association with classical cardiovascular risk factors]. / Incidencia de cardiopatía isquémica en el estudio HERMEX y su asociación con los factores de riesgo cardiovascular clásicos.

OBJECTIVES: Knowledge about the incidence of coronary heart disease in our country is scarce and its sources are not comparable. Our aim was to determine the incidence of ischemic heart disease in a population cohort in a 7 years of follow-up, as well as the risk associated with the different classical cardiovascular risk factors. METHODS: Cohort study with a population sample of 2833 subjects, selected by the simple random method in a population between 25 and 79, from the Don Benito - Villanueva de la Serena (Badajoz) health area, response rate was 80.5%. All episodes of angina pectoris, lethal and non-lethal myocardial infarction were collected in individuals with no previous history of cardiovascular disease. Cumulative incidences and incidence rates adjusted per 100,000 person-years by sex and overall were calculated. RESULTS: From 2833 initial cohort participants, 103 were excluded due to a history of cardiovascular disease and 61 for losses, 2669 completed the follow-up (94.2%). The median follow-up was 6.9 years (IR 6.5-7.5), 56.4% women; 59 events were recorded. The overall incidence rate of ischemic heart disease was 327 cases/100,000 person-years, corresponding to 470 cases/100,000 for men and 211 cases/100,000 people-years for women. The classical cardiovascular risk factors that were associated with a higher risk of presenting events in the follow-up were dyslipidemia and arterial hypertension, in addition to male sex and age. CONCLUSIONS: The incidence of ischemic heart disease in the urban-rural population of Extremadura is high. The classical cardiovascular risk factors most strongly associated with events were dyslipidemia, and arterial hypertension.

Nutrición, gastronomía y salud en la comunidad de Castilla y León / Nutrition, gastronomy and health in the community of Castilla y León

Introducción: la gastronomía y los hábitos alimentarios determinan el estado nutricional y de salud de una población. Las peculiaridades geográficas y climatológicas de Castilla y León (CyL) contribuyen al desarrollo de su riqueza cultural y gastronómica. Objetivos: analizar las características gastronómicas de CyL y evaluar las necesidades nutricionales y de salud de la población. Métodos: este estudio es una revisión narrativa. Resultados: en CyL existen más de 50 alimentos acogidos a distintas figuras de calidad, desde legumbres, embutidos, quesos, frutas y hortalizas hasta empanadas y dulces. Asimismo, CyL posee la ratio más elevada de establecimientos de restauración de España. El análisis del perfil calórico revela la tendencia hacia una dieta desequilibrada con exceso de ingesta de lípidos y proteínas en detrimento del consumo de hidratos de carbono complejos. La evaluación del consumo alimentario muestra valores superiores a la media nacional de todos los grupos de alimentos, con especial atención a la carne y derivados, leche y derivados, huevos, cereales y legumbres. En relación con el estilo de vida, se observan mejores valores en los indicadores de sedentarismo, actividad física y obesidad en comparación con el resto de España. Conclusiones: la comunidad de Castilla y Léon posee unas características geográficas y de identidad cultural propias que la convierten en una región de referencia a nivel nacional en relación con la producción y comercialización de productos autóctonos de calidad. Los hábitos alimentarios están asociados con la gastronomía y contribuyen a la promoción de un buen estado nutricional y de nivel de vida de la población

Introduction: gastronomy and eating habits are key factors that determine a population's health and nutritional status. The geographical and climatic peculiarities of Castilla y León (CyL) contribute to the development of its cultural and gastronomic wealth. Objectives: to evaluate the gastronomic characteristics of CyL and assess the population's health and nutritional needs. Methods: this study is a narrative review. Results: in CyL there are more than 50 foods with various figures of quality, from vegetables, meats, cheeses and fruits to pasties and sweets. CyL has also the highest ratio of dining options from Spain. The caloric profile analysis reveals the trend towards an unbalanced diet with excess intake of lipids and proteins to the detriment of the consumption of complex carbohydrates. The assessment of food consumption shows higher values than the average national in all the food groups, with special attention to the meat and derivatives, milk and derived, eggs, cereals and legumes. With regard to lifestyle, best values in indicators of sedentarism, physical activity and obesity are observed in comparison with the rest of Spain. Conclusions: the region of Castilla y León has its own geographical and cultural characteristics that make it a region of reference at the national level in relation to the production and marketing of local products of quality. Eating habits are associated with gastronomy and contribute to the promotion of a good nutritional status and standard of living of the population

Effect of ascorbic and chondrogenic derived decellularized extracellular matrix from mesenchymal stem cells on their proliferation, viability and differentiation.

BACKGROUND: The development and application of biomaterials to promote stem cell proliferation and differentiation has undergone major expansion over the last few years. Decellularized stem cell matrix (DSCMs) represent bioactive and biocompatible materials which achieve similar characteristics of native extracellular matrix. DSCMs have given promising outcomes in generating novel cell culture substrates mimicking specific niche microenvironments in tissue engineering. AIMS: This research aims at producing two different DSCMs obtained from adipose derived mesenchymal stem cells and bone marrow mesenchymal stem cells, characterize them and evaluate the DSCMs bioactivity on mesenchymal stem cells. METHODS: DSCMs were produced using ascorbic or chondrogenic medium, which were then used as a scaffold for adipose derived mesenchymal stem cells and bone marrow mesenchymal stem cells, respectively. The biological characteristics of both types of DSCMs, including cell attachment, morphology, proliferation, viability, and chondrogenic and osteogenic differentiation were evaluated and compared. RESULTS: Differences between ascorbic derived-DSCMs and chondrogenic derived DSCMs were found. Chondrogenic derived-DSCMs remained compact and stronger during extraction and this made their handling easier. Ascorbic derived-DSCMs showed a different protein composition to chondrogenic-DSCMs. Bioactive characteristics analyzed were different depending on the cellular origin of DSCM and the method used to produce them. CONCLUSIONS: The DSCMs obtained in this work constitutes favorable structure- and growth factors providing a microenvironment which is very similar to that of native ECM, which results in enhanced biological potential of the MSCs and responsiveness to the induction of differentiation. We found differences between ascorbic derived-DSCMs and chondrogenic derived DSCMs. Our results suggest that the cell source used to produce DSCMs is highly related to the bioactive characteristics of DSCMs.

Numerical analysis of the pressure drop across highly-eccentric coronary stenoses: application to the calculation of the fractional flow reserve.

BACKGROUND: Fractional flow reverse (FFR) is the gold standard assessment of the hemodynamic significance of coronary stenoses. However, it requires the catheterization of the coronary artery to determine the pressure waveforms proximal and distal to the stenosis. On the contrary, computational fluid dynamics enables the calculation of the FFR value from relatively non-invasive computed tomography angiography (CTA). METHODS: We analyze the flow across idealized highly-eccentric coronary stenoses by solving the Navier-Stokes equations. We examine the influence of several aspects (approximations) of the simulation method on the calculation of the FFR value. We study the effects on the FFR value of errors made in the segmentation of clinical images. For this purpose, we compare the FFR value for the nominal geometry with that calculated for other shapes that slightly deviate from that geometry. This analysis is conducted for a range of stenosis severities and different inlet velocity and pressure waveforms. RESULTS AND CONCLUSIONS: The errors made in assuming a uniform velocity profile in front of the stenosis, as well as those due to the Newtonian and laminar approximations, are negligible for stenosis severities leading to FFR values around the threshold 0.8. The limited resolution of the stenosis geometry reconstruction is the major source of error when predicting the FFR value. Both systematic errors in the contour detection of just 1-pixel size in the CTA images and a low-quality representation of the stenosis surface (coarse faceted geometry) may yield wrong outcomes of the FFR assessment for an important set of eccentric stenoses. On the contrary, the spatial resolution of images acquired with optical coherence tomography may be sufficient to ensure accurate predictions for the FFR value.

Pre-Kidney Transplant Lower Extremity Impairment and Post-Kidney Transplant Mortality.

Prediction models for post-kidney transplantation mortality have had limited success (C-statistics ≤0.70). Adding objective measures of potentially modifiable factors may improve prediction and, consequently, kidney transplant (KT) survival through intervention. The Short Physical Performance Battery (SPPB) is an easily administered objective test of lower extremity function consisting of three parts (balance, walking speed, chair stands), each with scores of 0-4, for a composite score of 0-12, with higher scores indicating better function. SPPB performance and frailty (Fried frailty phenotype) were assessed at admission for KT in a prospective cohort of 719 KT recipients at Johns Hopkins Hospital (8/2009 to 6/2016) and University of Michigan (2/2013 to 12/2016). The independent associations between SPPB impairment (SPPB composite score ≤10) and composite score with post-KT mortality were tested using adjusted competing risks models treating graft failure as a competing risk. The 5-year posttransplantation mortality for impaired recipients was 20.6% compared to 4.5% for unimpaired recipients (p < 0.001). Impaired recipients had a 2.30-fold (adjusted hazard ratio [aHR] 2.30, 95% confidence interval [CI] 1.12-4.74, p = 0.02) increased risk of postkidney transplantation mortality compared to unimpaired recipients. Each one-point decrease in SPPB score was independently associated with a 1.19-fold (95% CI 1.09-1.30, p < 0.001) higher risk of post-KT mortality. SPPB-derived lower extremity function is a potentially highly useful and modifiable objective measure for pre-KT risk prediction.

The effect of bolus volume on laryngeal closure and UES opening in swallowing: Kinematic analysis using 320-row area detector CT study.

This study investigated the effects of three different volumes of honey-thick liquid on the temporal characteristics of swallowing. Twenty-six healthy subjects (15 males, 11 females) underwent 320-row area detector CT scan while swallowing 3, 10 and 20 mL of honey-thick liquid barium. Three-dimensional images were created at 10 images/s. Kinematic events involving six structures (velopharynx, hyoid bone, epiglottis, laryngeal vestibule (LV), true vocal cords (TVC), upper esophageal sphincter (UES)) and timing of bolus movement were timed using frame by frame analysis. The overall sequence of events did not differ across three volumes; however, increasing bolus volume significantly changed the onset and termination of events. The bolus head reached to pharynx and esophagus earlier and the duration of bolus passing through UES was significantly longer in 10 and 20 mL compared to 3 mL (P < .05). Consequently, the onset of UES opening was significantly earlier with increased volume (P < .05). LV and TVC closure occurred later in 20 mL compared to 3 mL (P < .05). These changes in motion of pharynx and larynx appeared to promote swallow safety by preventing aspiration, suggesting that anatomical structure movements adapt in response to bolus volume. Our findings also suggest that the pharyngeal swallow behaviours may be modified by afferents in the oral cavity. The three-dimensional visualization and quantitative measurements provided by 320-ADCT provide essential benchmarks for understanding swallowing, both normal and abnormal.

Relación entre la grasa corporal y la expresión de ira en personas que realizan ejercicio regularmente / Relacionamento entre gordura corporal e expressão de raiva em pessoas que se exercitam regularmente / Relationship between body fat mass and the expression of anger in people who practice exercise customarily

La actividad física proporciona beneficios, tanto a la población sana como enferma, pero también puede derivar en problemas psicológicos y emocionales como respuesta al estrés. Además, aquellos atletas con menor peso corporal presentan indicadores más elevados de depresión e ira. Se plantea determinar la relación de la grasa corporal sobre la expresión de ira y entender la relación entre distintos comportamientos psicológicos, en personas físicamente activas. 264 sujetos cumplimentaron el Inventario de Expresión de Ira Estado-Rasgo, versión 2, para el estudio sobre las características de la ira y sus efectos en la salud mental y física. Se tomaron medidas antropométricas (peso, talla, IMC, porcentaje de grasa corporal, masa libre de grasa). Se calcularon distintos percentiles en función del género y edad, clasificando a los participantes en tres grupos: percentil 55 de grasa corporal. Se analizaron distintos comportamientos en relación al STAXI-2 y a los distintos percentiles, pero sin encontrar diferencias significativas entre la ira y los tres grupos (AU)

Physical activity provides benefits, both to healthy as to ill population, but can also lead to psychological and emotional problems in response to stress. Furthermore, those athletes with lower body weight have higher indicators of depression and anger. We propose to relate body fat on the expression of anger and to understand the relationship between different psychological behaviors in physically active people. 264 subjects completed the Anger Expression Inventory State Trait version 2 (STAXI-2), which studies the characteristics of anger and its effects on mental and physical health. Anthropometric measurements (weight, height, BMI, percent body fat, fat-free mass) were taken. Various body fat percentiles, 55 were calculated according to gender and age, classifying participants into three percentile groups. Different behaviors were recorded in relation to STAXI-2 and percentiles, but with no significant differences between anger and those groups (AU)

A atividade física proporciona benefícios tanto para pessoas saudáveis como doentes, mas também pode levar a problemas psicológicos e emocionais, como resposta ao estresse. Além disso, os atletas com menor peso corporal têm indicadores mais altos de depressão e raiva. Prevê-se a determinar a influência da gordura corporal sobre a modulação do comportamento e entender a relação entre os vários comportamentos psicológicos entre as pessoas fisicamente ativas. 264 pessoas preencheram um questionário ad hoc, que incluiu Anger Expression Inventory State Trait version 2 (STAXI-2). Medidas antropométricas (peso, altura, IMC, percentual de gordura corporal, massa livre de gordura) foram tomadas. Vários percentis foram calculados por sexo e idade, classificando os participantes em três grupos: percentil 55 de gordura corporal. Diferentes comportamentos foram registrados em relação ao STAXI-2 e os vários percentis, mas sem diferenças significativas entre a raiva e os três grupos (AU)

Purification process for MUFA- and PUFA-based monoacylglycerols from edible oils.

Important health benefits have been attributed to monoacylglycerols (MAGs) due to their various physiological functions, owing to which they become candidates for use as functional foods in order to prevent the onset of certain diseases such as colon cancer. In this work, six edible oils, namely: olive, linseed, sunflower, evening primrose, DHASCO® and ARASCO® have been processed to obtain different MUFA- and PUFA- based MAGs. First, the oils were hydrolyzed by means of an enzymatic process using porcine pancreatic lipase and then the reaction products were fractionated by using a liquid chromatography column containing silica gel as stationary phase in order to purify the MAGs-enriched fraction. A second chromatography process was performed using silver nitrate coated silica gel as stationary phase, in order to obtain the different MUFA- and PUFA-based MAGs from the corresponding oils. Overall, MAGs based on oleic, linoleic, α-linolenic, γ-linolenic, arachidonic and docosahexaenoic acids have been isolated in high yields and purities (92.6, 97.4, 95.3, 90.9, 100 and 95.3% purity, respectively). Positional distribution was determined by means of 1H NMR, which revealed a mix of 1(3) and 2-MAGs in variable proportions in the different MAGs.

Anti-Interleukin-6 Receptor Tocilizumab for Severe Juvenile Idiopathic Arthritis-Associated Uveitis Refractory to Anti-Tumor Necrosis Factor Therapy: A Multicenter Study of Twenty-Five Patients.

OBJECTIVE: To assess the efficacy of tocilizumab (TCZ) for the treatment of juvenile idiopathic arthritis (JIA)-associated uveitis. METHODS: We conducted a multicenter study of patients with JIA-associated uveitis that was refractory to conventional immunosuppressive drugs and anti-tumor necrosis factor (anti-TNF) agents. RESULTS: We assessed 25 patients (21 female; 47 affected eyes) with a mean ± SD age of 18.5 ± 8.3 years. Uveitis was bilateral in 22 patients. Cystoid macular edema was present in 9 patients. Ocular sequelae found at initiation of TCZ included cataracts (n = 13), glaucoma (n = 7), synechiae (n = 10), band keratopathy (n = 12), maculopathy (n = 9), and amblyopia (n = 5). Before TCZ, patients had received corticosteroids, conventional immunosuppressive drugs, and biologic agents (median 2 [range 1-5]), including adalimumab (n = 24), etanercept (n = 8), infliximab (n = 7), abatacept (n = 6), rituximab (n = 2), anakinra (n = 1), and golimumab (n = 1). Patients received 8 mg/kg TCZ intravenously every 4 weeks in most cases. TCZ yielded rapid and maintained improvement in all ocular parameters. After 6 months of therapy, 79.2% of patients showed improvement in anterior chamber cell numbers, and 88.2% showed improvement after 1 year. Central macular thickness measured by optical coherence tomography in patients with cystoid macular edema decreased from a mean ± SD of 401.7 ± 86.8 µm to 259.1 ± 39.5 µm after 6 months of TCZ (P = 0.012). The best-corrected visual acuity increased from 0.56 ± 0.35 to 0.64 ± 0.32 (P < 0.01). After a median follow-up of 12 months, visual improvement persisted, and complete remission of uveitis was observed in 19 of 25 patients. Significant reduction in the prednisone dosage was also achieved. The main adverse effects were severe autoimmune thrombocytopenia in 1 patient, pneumonia and then autoimmune anemia and thrombocytopenia in 1 patient, and viral conjunctivitis and bullous impetigo in 1 patient. CONCLUSION: TCZ appears to be a useful therapy for severe refractory JIA-associated uveitis.

Phytochemical Composition and Antitumor Activities of New Salad Greens: Rucola (Diplotaxis tenuifolia) and Corn Salad (Valerianella locusta).

D. tenuifolia and V. locusta, two greens, were analyzed for active compounds and antitumor actions on colorectal cancer cells. Phenolics were determined by UHPLC-Orbitrap-MS; carotenoids and glucosinolates by HPLC-MS; and sterols and fatty acids by gas-liquid chromatography (GLC). For antitumor effects, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) tests were run on HT-29 colorectal cancer cells, and in CCD-18 untransformed enterocyte cells. Six main carotenoids were identified in both vegetables, while total carotenoids accounted for 3520 and 2970 µg · g(-1) dry weight in D. tenuifolia and V. locusta, respectively. Six phenolics were detected in D. tenuifolia (68,600 µg · g(-1) dry weight) and five in V. locusta (139,000 µg · g(-1) dry weight). Three glucosinolates (GSL) were found in D. tenuifolia (1960 µg · g(-1) dry wt. total). Low-polarity extracts from V. locusta and D. tenuifolia showed IC50 ~ 150 and ~200 µg · mL(-1) on HT-29 cells, while both plants lacked actions on CCD-18 cells. V. locusta inhibited HT-29 cancer cells viability more efficiently than D. tenuiofolia, but induced less cytotoxicity. This work highlights the importance of functional foods for colorectal cancer prevention.

Perfiles metabolómicos de sujetos sanos y con cáncer de pulmón. Influencia de la carga tabáquica / The metabolomics of healthy subjects and those with lung cancer: the influence of smoking

INTRODUCCIÓN: la aplicación de técnicas metabolómicas presenta un gran potencial para la búsqueda de posibles biomarcadores de diagnóstico precoz en numerosas enfermedades. El empleo de procedimientos metabolómicos basados en espectrometría de masas permite estudiar las modificaciones metabólicas subyacentes al cáncer de pulmón (CP) y la influencia de la carga tabáquica (CT), medida en paquetes-año, en los correspondientes perfiles metabólicos. METODOLOGÍA: se estudió el suero de 9 controles sanos (no fumadores), 6 enfermos de CP con carga tabáquica moderada (CT 70). Se analizaron los metabolitos mediante técnicas de espectrometría de masas de alta resolución (DI-ESI-QTOFMS). Los perfiles metabólicos obtenidos se sometieron a análisis estadístico multivariante (PCA, PLS-DA). RESULTADOS: los tres grupos de estudio mostraron perfiles metabólicos claramente diferentes, lo que permitió identificar algunos posibles biomarcadores. Los niveles de glutatión se encontraron disminuidos en muestras de suero de pacientes con CP, mientras que se incrementó el contenido de distintos fosfolípidos de membrana (PL). La mayoría de estas anormalidades metabólicas se acentuó en pacientes con una CT elevada. CONCLUSIONES: el análisis metabolómico en muestras de suero permitió diferenciar claramente entre sujetos sanos y pacientes con CP. Así mismo, se identificaron posibles biomarcadores para el diagnóstico del CP (relacionados con rutas previamente conocidas en el proceso del cáncer). Además, estas alteraciones se vieron influenciadas por la carga tabáquica, confirmando la importancia del tabaquismo como factor de riesgo primario en el desarrollo del CP

By using high resolution metabolomics, we obtained the metabolomic profiles for patients who smoked and had lung cancer (LC) and a healthy, non-smoker control (HC) group; we assessed the influence of smoking on said profiles. The results show a clear discrimination between the metabolomic profiles of both groups studied; the metabolites causing said difference could be determined. Moreover, differences were encountered between the metabolomic profiles of heavy smokers with lung cancer compared to moderate smokers. INTRODUCTION: theapplicationof metabolomic techniques offers extensive potential to search for possible biomarkers in the early detection of several diseases. Using metabolomic procedures based on mass spectrometry allow us to study underlying metabolic changes in lung cancer and the influence of smoking, measured as packets/year, in the corresponding metabolic profiles. METHOD: the serum from 9 healthy control subjects (nonsmokers) was studied, as well as that of 6 patients with lung cancer who were moderate smokers (CT 70). The metabolites were analyzed using high resolution mass spectrometer techniques (DI-ESI-QTOF-MS). The metabolic profiles obtained were subject to multivariate statistical analysis (PCA, PLS-DA). RESULTS: the three groups studied showed clearly differentiated metabolic profiles, which facilitated the identification of certain biomarkers. Glutathione levels were found to be decreased in the sample from patients with lung cancer, while the content of various membrane phospholipids increased. Most of these metabolic abnormalities were heightened in patients who were heavy smokers. CONCLUSIONS: the metabolomics analysis in serum samples clearly differentiated healthy subjects from patients with lung cancer. Also, possible biomarkers were identified to diagnose lung cancer (linked to previously known routes in the cancer process. Moreover, these alterations were influenced by the amount smoked, thus confirming the importance of smoking as a primary risk factor in developing lung cáncer

Study on viability and chondrogenic differentiation of cryopreserved adipose tissue-derived mesenchymal stromal cells for future use in regenerative medicine.

Adipose-derived mesenchymal stromal cells are promising as a regenerative therapy tool for defective tissues in mesenchymal lineage, including fat, bone, cartilage, and blood vessels. In potential future clinical applications, adipose-derived stem cell cryopreservation is an essential fundamental technology. The aim of this study is to define an adequate protocol for the cryopreservation of adipose-derived mesenchymal stromal cells, by comparing various protocols so as to determine the effects of cryopreservation on viability and chondrogenic differentiation potential of adipose-derived stem cells upon freeze-thawing of AT-MSCs colonies cryopreserved with standard and modified protocols, using flow cytometry and confocal microscopy. The study concludes that adipose-derived mesenchymal stromal cells could be long-term cryopreserved without any loss of their proliferative or differentiation potential.

Metal interactions in mice under environmental stress.

A metallomic analytical approach based on the use of size exclusion chromatography coupled to ICP-MS has been used to obtain metal profiles related to overexpression or inhibition of metal-binding biomolecules, which is connected to exposure experiment of laboratory mice Mus musculus to toxic metals, such as Cd, Hg and As. Exposure to Cd induces the formation of Cd-metallothionein in liver that reveals the protective role of this organ; however, exposure to Hg reduces the intensity of the peak associated to Cu-superoxide dismutase (Cu-SOD) while Hg-SOD peak increases, which suggests the competence of Cu and Hg for the active sites of SOD in liver that causes mercury translocation to kidney, in which the concentration of Hg as Hg-metallothionein increases drastically to be excreted by urine. It has been also observed the protective effect of selenium on mercury toxicity in blood plasma, which produces decreasing of the intensity of Se-protein in plasma with Hg exposure and correlative increases of Hg-albumin that transport mercury to kidney for excretion. Finally, arsenic exposure provokes the accumulation of small metabolites of this element, such as dimethylarsenic and monomethylarsenic for excretion. The application of the metallomic approach to liver extracts from free-living mouse Mus spretus shows the overexpression of Cu, Zn and Cd-peaks at 7 kDa (related to metal-metallothionein) in environmental contaminated sites, as well as the increase of peaks related to Cu- and Zn-SOD and Zn-albumin. However, in kidney, can be checked the presence of high concentration of arsenic small metabolites in contaminated areas, similarly to results found in exposure experiments. In addition, the application of a metabolomic approach based on direct infusion mass spectrometry to organ extracts (liver, kidney and serum) from mice (M. musculus) exposed to arsenic reveals important metabolic changes related to antioxidative activity, membrane cell damage, energy metabolism and arsenic elimination. Similar results were obtained from free-living mouse (M. spretus) from areas contaminated with arsenic. The integration of metallomics and metabolomics results provides a more comprehensive evaluation about the biological response in exposure experiments to toxic metals as well as in environmental assessment of contamination.

Biological response of free-living mouse Mus spretus from Doñana National Park under environmental stress based on assessment of metal-binding biomolecules by SEC-ICP-MS.

A metallomic approach based on the use of size-exclusion chromatography (Superdex-75) with inductively coupled plasma mass spectrometry (ICP-MS) detection is combined with anion or cation exchange chromatography to characterize the biological response of the free-living mouse Mus spretus. The approach has been applied to contaminated and non-contaminated areas from Doñana National Park (southwest Spain) and the surroundings. Several areas affected by differential contamination from mining, industrial, and agricultural activities have been considered. The high presence of Mn, Cu, and Zn in liver and As and Cd in kidney is remarkable, especially in contaminated areas. The size exclusion chromatograms traced by Mn in liver cytosolic extracts are more intense than in kidney; a Mn-peak matching with the standard of 32 kDa (superoxide dismutase) is present in these organs, and its intensity is correlated with the concentration of Mn in the extracts. High-intensity peaks traced by Cu, Zn, and Cd at 7 kDa (matching with metallothionein I standard) in liver extract are triggered by the presence of contaminants. Other peaks related with molecules of 32 and 67 kDa traced by Cu and Zn can also be observed, although their intensity is higher in sites with low contamination. In kidney extracts, the presence of a Cd-peak with Mr of 7 kDa (tentatively Cd-metallothionein) with high intensity under the action of contaminants was observed, but high biological responses are also proven in the protected area of the Park, which denotes a progressive increase of diffuse contamination.

Biological responses related to agonistic, antagonistic and synergistic interactions of chemical species.

The fact that the essential or toxic character of elements is species specific has encouraged the development of analytical strategies for chemical speciation over the last twenty years; indeed, there are now a great number of them that provide very good performance. However, biological systems are exposed to a complex environment in which species of elements can interact in a synergistic/antagonistic fashion. Thus, the metabolism of trace elements cannot be considered in isolation. On the other hand, biological systems are dynamic, so it is necessary to study the trafficking of species of elements between organs, tissues or cell compartments in order to decipher the biochemical processes of the interactions in which they are involved. Although the application of liquid chromatography-inductively coupled plasma-based "metallomics" methods in combination with organic mass spectrometry can provide much-needed insight, new analytical strategies are required to really understand the role of species of elements in biological systems and the mechanisms of their interactions. In the present paper, the interactions of the most widely studied elements in this context (Se, Hg and As) are discussed, as well as other important interactions between different elements.

[Role of genetics in the etiology of synucleinopathies]. / Papel de la genética en la etiología de las sinucleinopatías.

The protein family known as synucleins is composed of α-, ß- and γ-synuclein. The most widely studied is the α-synuclein protein due to its participation in essential processes of the central nervous system. Neurotoxicity of this protein is related to the presence of multiplications (duplications and triplications) and point mutations in the gene sequence of the α-synuclein gene (SNCA), differential expression of its isoforms and variations in post-transductional modifications. Neurotoxicity is also related to cytoplasmic inclusions known as Lewy bodies (LBs) and Lewy neurites (LNs), which are also present in α-synucleinopathies. In general, the ß-synuclein protein, codified by the SNCB gene, acts as a regulator of processes triggered by α-synuclein and its function is altered by variations in the gene sequence, while γ-synuclein, codified by the SNCG gene, seems to play a major role in certain tumoral processes.

Molecular mass spectrometric identification of superoxide dismutase in the liver of mice Mus musculus and Mus spretus using a metallomics analytical approach.

This paper reports the identification and quantification of superoxide dismutase in the liver of Mus musculus and Mus spretus mice using a metallomics analytical approach. The approach consisted of using orthogonal chromatographic systems coupled to ICP-MS and UV detectors. Size-exclusion fractionation of the cytosolic extracts was followed by anion-exchange chromatographic separation of Cu- and Zn-containing species. After purification then tryptic digestion, Cu- and Zn-containing superoxide dismutase was identified by nESI-QqTOF. The MS-MS spectra of doubly charged peptides, with the Mascot searching engine, were used to obtain the sequence of the protein.