Fundación Pública Andaluza para la Investigación Biosanitaria de Andalucía Oriental - Alejandro Otero (FIBAO)

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  • Publication
    Combined use of UV and MS data for ICH Stability-Indication Method: Quantification and isoforms identification of intact nivolumab
    (Elsevier, 2022-08-31) Torrente-Lopez, Anabel; Hermosilla, Jesus; Perez-Robles, Raquel; Salmeron-Garcia, Antonio; Cabeza, Jose; Navas, Natalia; [Torrente-Lopez, Anabel] Univ Granada, Biomed Res Inst Ibs Granada, Sci Fac, Dept Analyt Chem, E-18071 Granada, Spain; [Hermosilla, Jesus] Univ Granada, Biomed Res Inst Ibs Granada, Sci Fac, Dept Analyt Chem, E-18071 Granada, Spain; [Perez-Robles, Raquel] Univ Granada, Biomed Res Inst Ibs Granada, Sci Fac, Dept Analyt Chem, E-18071 Granada, Spain; [Navas, Natalia] Univ Granada, Biomed Res Inst Ibs Granada, Sci Fac, Dept Analyt Chem, E-18071 Granada, Spain; [Perez-Robles, Raquel] Junta Andalucia, Fdn Invest Biosanitaria Andalucia Oriental Alejan, Granada, Spain; [Salmeron-Garcia, Antonio] San Cecilio Univ Hosp Granada, Biomed Res Inst Ibs Granada, UGC Hosp Pharm, E-18012 Granada, Spain; [Cabeza, Jose] San Cecilio Univ Hosp Granada, Biomed Res Inst Ibs Granada, UGC Hosp Pharm, E-18012 Granada, Spain; Ministry of Universities, Spain; Junta de Andalucia (Spain); European Regional Develop-ment Funds; Junta de Andalucia, Spain; I + D + i-Junta de Andalucia, Spain; Universidad de Granada, Proyectos I +D +i del Programa Operativo FEDER Andalucia 2020; European Regional Development Funds; CBUA/Universidad de Granada
    Nivolumab (Opdivo (R)) is a fully human immunoglobulin G4 isotype approved for the treatment of many cancers. It acts as an immune checkpoint inhibitor by blocking the interaction between PD-1 (Programmed Cell Death Protein 1) - an inhibitory receptor expressed on activated T cells- and its ligands, PD-L1 and PD-L2. The quantification of therapeutic proteins in their medicines and pharmaceutical preparations remains challenging because the protein content, a critical quality attribute, must be rigorously calculated using a validated stabilityindicating method, such as that indicated by the International Conference on Harmonization (ICH) quality guidelines, and this requires the analysis of the drug in the presence of its degraded products. In this work, we present an strategy based on the combined use of the UV and MS data to full file the requirement of the ICH-Q2 (R1) to develop and validated as stability indicated a (RP)UHPLC/UV-(HESI/OrbitrapTM)MS method for the quantification of nivolumab in medicinal products. A comparative study of all figures of merit of the method using UV or MS data are shown and discussed. The results show that linearity was similar for the two detectors and was established over a range of 4-45 mu g/mL and 1-45 mu g/mL for the UV and (HESI/OrbitrapTM)MS signals, respectively. The sensitivity of the method was higher when using the (HESI/OrbitrapTM)MS signal (0.2 mu g/mL) than with the UV(2.0 mu g/mL). However, the UV signal provided better accuracy and precision than the (HESI/ OrbitrapTM)MS signal, which did not meet the criteria for method robustness and system suitability. In spite of this, the MS signal plays a crucial role in this methodology by obtaining the molecular weight profile of the nivolumab isoforms, so enabling us to propose the glycans profile and detect structural modification due to degradation. The specificity of the method was evaluated by conducting forced degradation tests on samples of nivolumab in medicine form. The aim was to find out whether nivolumab suffers structural modifications when subject to stress. Structural modifications were detected by analysing the MS isoform profile, as changes of this kind promote new isoforms that are not chromatographically separated or detected by the UV signal. In this way, we demonstrated that the (RP)UHPLC/UV-(HESI/OrbitrapTM)MS method was capable of detecting nivolumab degradation, and was suitable for use in nivolumab stability studies. Thus, the protein content in the daily surplus of the Opdivo (R) medicine, stored either at room temperature (20 degrees C) or refrigerated at 4 degrees C, could be tracked for 15 days.
  • Publication
    Tracking the physicochemical stability of teduglutide (Revestive®) clinical solutions over time in different storage containers.
    (2022-09-17) Pérez-Robles, Raquel; Hermosilla, Jesús; Navas, Natalia; Clemente-Bautista, Susana; Jiménez-Lozano, Inés; Cabañas-Poy, Maria Josep; Ruiz-Travé, Julio; Hernández-García, María Amparo; Cabeza, Jose; Salmerón-García, Antonio
    Teduglutide, the active ingredient of the medicine Revestive® (5 mg), is a recombinant therapeutic peptide that mimics the effects of the endogenous glucagon-like peptide 2 (GLP-2). It stimulates intestinal growth, adaptation and function in patients with Short Bowel Syndrome who are dependent on parenteral nutrition. The Summary of Product Characteristics recommends immediate use of the reconstituted solutions and the discarding of any subsequent surplus. This study aims to carry out a long-term stability study that reproduces hospital conditions of use which provide sound evidence regarding the use of teduglutide surplus beyond the Summary Product Characteristics recommendations. We conducted a stability study of teduglutide solutions prepared from a 5 mg vial of Revestive®. Some of the solutions were stored in their original vial after reconstitution, while others were repackaged in plastic syringes to evaluate their physicochemical stability over time. For this purpose, we applied a set of previously validated analytical methodologies to evaluate the main critical quality attributes of teduglutide, i.e., primary (including post-tralational modifications), secondary and tertiary structures, aggregates, particulate, concentration and pH. The results indicate that the solutions maintain high physicochemical stability over time, regardless of the storage temperature (4ºC or -20ºC) or the storage container (vials or syringes). This research provides new data on the stability of Revestive® that will be of great value to hospital pharmacists. This comprehensive assessment of the physicochemical long-term stability of TGT has demonstrated that under the storage conditions and over the period studied here, the medicine maintains its quality, efficacy and safety profiles.
  • Publication
    Degradation and in-use stability study of five marketed therapeutic monoclonal antibodies by generic weak cation exchange liquid chromatographic method ((WCX)HPLC/DAD).
    (2022-05-18) Martínez-Ortega, Antonio; Herrera, Agustín; Salmerón-García, Antonio; Cabeza, José; Perez-Robles, Raquel; Navas, Natalia
    Therapeutic monoclonal antibodies (mAbs) represent a very important class of the current biopharmaceutics. The great complexity of their structure made necessary the use of different analytical approaches for assessing different physico-chemical properties. In this work, weak cation exchange (WCX) high performance liquid chromatography with diode array detection ((WCX)HPLC/DAD) is used to assess the charge variant profile. The method here developed combined the effect of ionic strength and controlled pH gradient and allows for the charge variants analysis of the five mAbs studied, namely bevacizumab (BVZ), cetuximab (CTX) infliximab (INF), rituximab (RTX) and trastuzumab (TTZ), which are among the most used mAbs worldwide. The differences in the charge variants in the natural isoforms of the mAbs promoted characteristic WCX chromatograms for each of mAbs that can be also useful for identification purposes. These chromatograms have provided to be suitable for tracking changes in the charge variants of each mAb analyzed both in controlled degraded and in stabilities study along time of in-use samples solutions at 2 mg/mL in 0.9% NaCl stored refrigerated (at 4 °C) and frozen (-20 °C) for two months. The results obtained indicated different stabilities of these mAbs, all IgG1, against degradation by different stressed environmental conditions and in-use stability along two months.
  • Publication
    [Assessment and follow-up of patients with suspected COVID-19 in the first pandemic wave in an urban area of Andalusia (Spain)].
    (2021-07-16) Pérez-Milena, Alejandro; Leyva-Alarcón, Ana; Barquero-Padilla, Raquel M; Peña-Arredondo, Melody; Navarrete-Espinosa, Cristóbal; Rosa-Garrido, Carmen
    To know the characteristics of the initial care and telephone follow-up of patients with suspected COVID-19 in the first wave of the pandemic. Observational, retrospective (audit of medical records). Urban Primary Care Center of Andalusia (Spain). Probable cases of SARS-CoV-2 (from 20/03/15 to 20/06/15). Initial medical assessment (place and modality) and telephone follow-up (number of calls and duration). Sociodemographic variables (including family structure). Clinical course (symptoms, vulnerability, tests, hospital admission and outcome). Three hundred one patients (51.5±17.8 years; 23% vulnerable people; 17% non-nuclear family structure). First assessment in Primary Care by phone (59.8%) and face-to-face (25.2%). At the hospital emergency department (11%), patients were more frequently from non-nuclear families (P Population chose to be attended in Primary Care during the pandemic first wave, above all by phone. Telephone follow-up was well accepted and useful to select patients with serious complications. Initial medical assessment in the hospital emergency department was related to a lack of social support but not with greater clinical severity.
  • Publication
    Immune checkpoint inhibitors-associated thrombosis in patients with lung cancer and melanoma: a study of the Spanish society of medical oncology (SEOM) thrombosis and cancer group.
    (2022-06-06) Cánovas, Manuel Sánchez; Garay, David Fernández; Moran, Laura Ortega; Pérez, Jaime Rubio; Rubio, Carlos Miguel Guirao; de Mena, Miriam Lobo; Portero, Berta Obispo; Castro, Jesús Brenes; Lage, Yolanda; Lavin, Diego Cacho; Blanco, Ana Belen Rupérez; de Soignie, Ana Manuela Martín Fernández; Perejón, Jonatan Zacarías Benoit; Colomo, Laura Jiménez; Boluda, Noel Blaya; Moreno, Javier Bosque; Verduguez, Teresa Quintanar; Garrido, Carmen Rosa; Huertas, Roberto Martín; Puig, Carme Font I; Martín, Andrés Jesús Muñoz
    Immune Checkpoint Inhibitors (ICI) can be associated with thrombotic events, both venous and arterial (VTE/AT). However, there is a paucity of information regarding patients in routine clinical practice. Retrospective, multicenter study promoted by the Thrombosis and Cancer Section of the Spanish Society of Medical Oncology (SEOM). Patients with melanoma and lung cancer who initiated ICI between 01/01/2015 and 31/12/2019 were recruited. Minimum follow-up was 6 months (unless it was not possible because of death). The primary objective was to calculate the incidence of ICI-associated VTE/AT and the secondary objectives included to analyze its impact on survival and to identify predictor variables for VTE/AT. 665 patients with lung cancer were enrolled. The incidence of VTE/AT during follow-up was 8.4%. Median overall survival (OS) was lower in the VTE/AT group (12 months 95% CI 4.84-19.16 vs. 19 months 95% CI 16.11-21.9; p = 0.0049). Neutrophil/lymphocyte ratio (NLR) and anemia upon initiation of IT, as well as a history of thrombosis between cancer diagnosis and the start of ICI, were predictive variables for developing of VTE/AT (p  ICI increases the risk of VTE/AT in patients with lung cancer and melanoma, which impact OS.
  • Publication
    Isogenic GAA-KO Murine Muscle Cell Lines Mimicking Severe Pompe Mutations as Preclinical Models for the Screening of Potential Gene Therapy Strategies.
    (2022-06-04) Aguilar-González, Araceli; González-Correa, Juan Elías; Barriocanal-Casado, Eliana; Ramos-Hernández, Iris; Lerma-Juárez, Miguel A; Greco, Sara; Rodríguez-Sevilla, Juan José; Molina-Estévez, Francisco Javier; Montalvo-Romeral, Valle; Ronzitti, Giuseppe; Sánchez-Martín, Rosario María; Martín, Francisco; Muñoz, Pilar
    Pompe disease (PD) is a rare disorder caused by mutations in the acid alpha-glucosidase (GAA) gene. Most gene therapies (GT) partially rely on the cross-correction of unmodified cells through the uptake of the GAA enzyme secreted by corrected cells. In the present study, we generated isogenic murine GAA-KO cell lines resembling severe mutations from Pompe patients. All of the generated GAA-KO cells lacked GAA activity and presented an increased autophagy and increased glycogen content by means of myotube differentiation as well as the downregulation of mannose 6-phosphate receptors (CI-MPRs), validating them as models for PD. Additionally, different chimeric murine GAA proteins (IFG, IFLG and 2G) were designed with the aim to improve their therapeutic activity. Phenotypic rescue analyses using lentiviral vectors point to IFG chimera as the best candidate in restoring GAA activity, normalising the autophagic marker p62 and surface levels of CI-MPRs. Interestingly, in vivo administration of liver-directed AAVs expressing the chimeras further confirmed the good behaviour of IFG, achieving cross-correction in heart tissue. In summary, we generated different isogenic murine muscle cell lines mimicking the severe PD phenotype, as well as validating their applicability as preclinical models in order to reduce animal experimentation.
  • Publication
    Predictive Model and Mortality Risk Score during Admission for Ischaemic Stroke with Conservative Treatment.
    (2022-03-08) Lea-Pereira, María Carmen; Amaya-Pascasio, Laura; Martínez-Sánchez, Patricia; Rodríguez Salvador, María Del Mar; Galván-Espinosa, José; Téllez-Ramírez, Luis; Reche-Lorite, Fernando; Sánchez, María-José; García-Torrecillas, Juan Manuel
    Stroke is the second cause of mortality worldwide and the first in women. The aim of this study is to develop a predictive model to estimate the risk of mortality in the admission of patients who have not received reperfusion treatment. A retrospective cohort study was conducted of a clinical-administrative database, reflecting all cases of non-reperfused ischaemic stroke admitted to Spanish hospitals during the period 2008-2012. A predictive model based on logistic regression was developed on a training cohort and later validated by the "hold-out" method. Complementary machine learning techniques were also explored. The resulting model had the following nine variables, all readily obtainable during initial care. Age (OR 1.069), female sex (OR 1.202), readmission (OR 2.008), hypertension (OR 0.726), diabetes (OR 1.105), atrial fibrillation (OR 1.537), dyslipidaemia (0.638), heart failure (OR 1.518) and neurological symptoms suggestive of posterior fossa involvement (OR 2.639). The predictability was moderate (AUC 0.742, 95% CI: 0.737-0.747), with good visual calibration; Pearson's chi-square test revealed non-significant calibration. An easily consulted risk score was prepared. It is possible to create a predictive model of mortality for patients with ischaemic stroke from which important advances can be made towards optimising the quality and efficiency of care. The model results are available within a few minutes of admission and would provide a valuable complementary resource for the neurologist.
  • Publication
    Identification of Potential Targets Linked to the Cardiovascular/Alzheimer's Axis through Bioinformatics Approaches.
    (2022-02-06) Andújar-Vera, Francisco; García-Fontana, Cristina; Sanabria-de la Torre, Raquel; González-Salvatierra, Sheila; Martínez-Heredia, Luis; Iglesias-Baena, Iván; Muñoz-Torres, Manuel; García-Fontana, Beatriz
    The identification of common targets in Alzheimer's disease (AD) and cardiovascular disease (CVD) in recent years makes the study of the CVD/AD axis a research topic of great interest. Besides aging, other links between CVD and AD have been described, suggesting the existence of common molecular mechanisms. Our study aimed to identify common targets in the CVD/AD axis. For this purpose, genomic data from calcified and healthy femoral artery samples were used to identify differentially expressed genes (DEGs), which were used to generate a protein-protein interaction network, where a module related to AD was identified. This module was enriched with the functionally closest proteins and analyzed using different centrality algorithms to determine the main targets in the CVD/AD axis. Validation was performed by proteomic and data mining analyses. The proteins identified with an important role in both pathologies were apolipoprotein E and haptoglobin as DEGs, with a fold change about +2 and -2, in calcified femoral artery vs healthy artery, respectively, and clusterin and alpha-2-macroglobulin as close interactors that matched in our proteomic analysis. However, further studies are needed to elucidate the specific role of these proteins, and to evaluate its function as biomarkers or therapeutic targets.
  • Publication
    Method for identification and quantification of intact teduglutide peptide using (RP)UHPLC-UV-(HESI/ORBITRAP)MS.
    (2022-11-10) Pérez-Robles, Raquel; Salmerón-García, Antonio; Clemente-Bautista, Susana; Jiménez-Lozano, Inés; Cabañas-Poy, María Josep; Cabeza, Jose; Navas, Natalia
    Teduglutide (Revestive®, 10 mg mL-1) is a recombinant human glucagon-like peptide 2 analogue, used in the treatment of short bowel syndrome, a serious and highly disabling condition which results from either too small a length of intestine or loss of critical intestinal function. The determination of therapeutic compounds of protein-nature is always challenging due to their complex structure. In this work, we present a fast, straightforward reversed phase (RP)UHPLC-UV-(HESI/ORBITRAP)MS method for the identification and quantification of the intact teduglutide peptide. The method has been developed and validated in accordance with the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines; therefore, linearity, limits of detection and quantification, accuracy (precision and trueness), robustness, system suitability and specificity using the signal from the UV and MS, have been evaluated. The validation performance parameters obtained from the UV and MS signals were compared throughout the work, to select the most suitable. To study the specificity of the method and the impact of medicine mishandling under hospital conditions, force degradation studies were performed, i.e. thermal (40 °C and 60 °C), shaking (mechanical) and light (accelerated exposition) effects. Identification by the exact mass of teduglutide was achieved and it was confirmed that the peptide does not undergo any post-translational modifications (PTMs). To the best of our knowledge, the present work reports the first method developed for the simultaneous identification, structural characterization, and quantification of the therapeutic teduglutide peptide. Finally, the proposed method is able to indicate stability when quantifying the intact teduglutide since detects and characterises the exact mass of the degradation/modification products.
  • Publication
    Pomalidomide in the treatment of multiple myeloma: design, development and place in therapy.
    (2017-08-22) Ríos-Tamayo, Rafael; Martín-García, Agustín; Alarcón-Payer, Carolina; Sánchez-Rodríguez, Dolores; de la Guardia, Ana María Del Valle Díaz; García Collado, Carlos Gustavo; Jiménez Morales, Alberto; Jurado Chacón, Manuel; Cabeza Barrera, José
    Multiple myeloma is a very heterogeneous disease with variable survival. Despite recent progress and the widespread use of new agents, patients with relapsed and refractory disease have a poor outcome. Immunomodulatory drugs play a key role in both the front-line and the relapsed/refractory setting. The combination of pomalidomide (POM) and dexamethasone is safe and effective in relapsed and refractory patients, even in those with high-risk cytogenetic features. Furthermore, it can be used in most patients without the need to adjust according to the degree of renal failure. In order to further improve the results, POM-based triplet therapies are currently used. This article highlights the most relevant issues of POM and POM-based combinations in the relapsed/refractory multiple myeloma setting, from a pharmacological and clinical point of view.
  • Publication
    Impact of vaccination uptake on hospitalizations due to rotavirus acute gastroenteritis in 2 different socioeconomic areas of Spain
    (Taylor & francis inc, 2016-01-01) Gimenez Sanchez, Francisco; Jimenez Nogueira, Esperanza; Sanchez Forte, Miguel; Ibanez Alcalde, Mercedes; Cobo, Elvira; Angulo, Raquel; Garrido Fernandez, Pablo; [Gimenez Sanchez, Francisco] Hosp Torrecardenas, Unidad Infectol Pediat, Inst Balmis Vacunas, Almeria, Spain; [Gimenez Sanchez, Francisco] Inst Hispalense Pediat, Granada, Spain; [Jimenez Nogueira, Esperanza] Hosp Torrecardenas, Dept Pediat, Almeria, Spain; [Sanchez Forte, Miguel] Hosp Torrecardenas, Dept Pediat, Almeria, Spain; [Cobo, Elvira] Hosp Torrecardenas, Dept Pediat, Almeria, Spain; [Ibanez Alcalde, Mercedes] Hosp Poniente, Almeria, Spain; [Angulo, Raquel] Hosp Poniente, Almeria, Spain; [Garrido Fernandez, Pablo] FIBAO, Almeria, Spain
    Rotavirus is the leading cause of hospitalization due to acute gastroenteritis (AGE) in infants and toddlers. However, rotavirus vaccination has been associated with a decline in hospitalization rates due to rotavirus AGE.A descriptive retrospective study was conducted to analyze the impact of rotavirus vaccination on the rate of hospitalizations due to AGE among children 2years old in 2 areas of the province of Almeria, Spain. After eight years of rotavirus vaccination, rates of hospitalizations due to rotavirus AGE are diminished. This decline is closely related to vaccine coverage in the studied areas.
  • Publication
    May bioactive compounds from the olive fruit improve the postprandial insulin response in healthy adults?
    (Elsevier, 2021-06-02) Sanchez-Rodriguez, Estefania; Alejandra Vazquez-Aguilar, Laura; Biel-Glesson, Sara; Ramon Fernandez-Navarro, Jose; Antonio Espejo-Calvo, Juan; Maria Olmo-Peinado, Jose; de la Torre, Rafael; Fito-Colomer, Monserrat; Isabel Covas, Maria; Romero, Concepcion; Brenes, Manuel; Martinez de Victoria, Emilio; Gil, Angel; Dolores Mesa, Maria; [Sanchez-Rodriguez, Estefania] Univ Granada, Biomed Res Ctr, Inst Nutr & Food Technol Jose Mataix, Dept Biochem & Mol Biol 2, Parque Tecnol Salud,Ave Conocimiento S-N, Granada 18100, Spain; [Alejandra Vazquez-Aguilar, Laura] Univ Granada, Biomed Res Ctr, Inst Nutr & Food Technol Jose Mataix, Dept Biochem & Mol Biol 2, Parque Tecnol Salud,Ave Conocimiento S-N, Granada 18100, Spain; [Gil, Angel] Univ Granada, Biomed Res Ctr, Inst Nutr & Food Technol Jose Mataix, Dept Biochem & Mol Biol 2, Parque Tecnol Salud,Ave Conocimiento S-N, Granada 18100, Spain; [Dolores Mesa, Maria] Univ Granada, Biomed Res Ctr, Inst Nutr & Food Technol Jose Mataix, Dept Biochem & Mol Biol 2, Parque Tecnol Salud,Ave Conocimiento S-N, Granada 18100, Spain; [Biel-Glesson, Sara] Fdn Publ Andaluza Invest Biosanitaria Andalucia O, Ave Madrid 15, Granada 18001, Spain; [Ramon Fernandez-Navarro, Jose] Fdn Publ Andaluza Invest Biosanitaria Andalucia O, Ave Madrid 15, Granada 18001, Spain; [Antonio Espejo-Calvo, Juan] Inst Calidad & Seguridad Alimentaria ICSA TECNOFO, Granada, Spain; [Maria Olmo-Peinado, Jose] Acer Campestres SL, Almendro 37, Jaen 23670, Spain; [de la Torre, Rafael] Hosp del Mar Res Inst IMIM, Integrat Pharmacol & Syst Neurosci Res Grp, Dr Aiguader 88, Barcelona 08003, Spain; [de la Torre, Rafael] Hlth Inst Carlos III, Spanish Biomed Res Networking Ctr Physiopathol Ob, Monforte de Lemos 3-5, Madrid 28029, Spain; [Fito-Colomer, Monserrat] Hlth Inst Carlos III, Spanish Biomed Res Networking Ctr Physiopathol Ob, Monforte de Lemos 3-5, Madrid 28029, Spain; [Gil, Angel] Hlth Inst Carlos III, Spanish Biomed Res Networking Ctr Physiopathol Ob, Monforte de Lemos 3-5, Madrid 28029, Spain; [Fito-Colomer, Monserrat] Hosp del Mar Res Inst IMIM, Cardiovasc Risk & Nutr Res Grp, Dr Aiguader 88, Barcelona 08003, Spain; [Isabel Covas, Maria] Handesbolag NUPROAS HB, NUPROAS Nutr Project Assessment, Nacka, Sweden; [Romero, Concepcion] Univ Campus Pablo de Olavide, Food Biotechnol Dept Inst Grasa IG CSIC, Bldg 46,Ctra Utrera Km 1, Seville 41013, Spain; [Brenes, Manuel] Univ Campus Pablo de Olavide, Food Biotechnol Dept Inst Grasa IG CSIC, Bldg 46,Ctra Utrera Km 1, Seville 41013, Spain; [Martinez de Victoria, Emilio] Univ Granada, Biomed Res Ctr, Inst Nutr & Food Technol Jose Mataix, Dept Physiol, Parque Tecnol Salud,Ave Conocimiento S-N, Granada 18100, Spain; [Gil, Angel] Ibs GRANADA, Biosanit Res Inst Granada, Granada 18014, Spain; [Dolores Mesa, Maria] Ibs GRANADA, Biosanit Res Inst Granada, Granada 18014, Spain; University of Granada (Spain); University of Guadalajara (Mexico); I + D FEDER-INTERCONNECTA (CDTI); Junta de Andalucia, Spain; ACER CAMPESTRES S.L.; SAN FRANCISCO DE ASIS Coop; AGROINSUR S.L.
    Scope. The postprandial effects of virgin olive oils (VOOs) enriched with phenolic compounds and triterpenes from the olive fruit on plasma glucose and insulin (primary outcomes), and gastrointestinal hormones responses were evaluated in healthy adults. Methods and results: Single doses (30 mL) of three oils were evaluated: optimized polyphenols-rich VOO (OVOO); functional olive oil (FOO): OVOO enriched with triterpene acids; and VOO with low content of polyphenols. Postprandial plasma insulin release was lower after the intake of the FOO compared to VOO, while plasma glucose levels were lower after the intake of the VOO compared to OVOO. Matsuda's index of insulin sensitivity improved after the intake of FOO and OVOO, while the insulinogenic index and gastric inhibitory polypeptide (GIP) tended to improve after the intake of OVOO. Conclusion: The enrichment of VOOs with bioactive compounds from the olive fruit increases its benefits, improving postprandial insulin release and peripheral tissue sensitivity.
  • Publication
    Differences in Dietary Habits, Physical Exercise, and Quality of Life between Patients with Obesity and Overweight.
    (2021-07-20) Herrera-Espiñeira, Carmen; de Pascual Y Medina, Ana María; López-Morales, Manuel; Díaz Jiménez, Paloma; Rodríguez Ruiz, Antonia; Expósito-Ruiz, Manuela
    Overweight and obesity differ in their repercussions on the health and health-related quality of life (HRQoL) of patients. The objective of this study was to compare physical activity levels and dietary habits before admission and HRQoL at discharge between patients with obesity and overweight. A cross-sectional study was undertaken among participants in a clinical trial on education for healthy eating and physical activity, enrolling non-diabetic patients admitted to Internal Medicine Departments. These were classified by body mass index (BMI) as having overweight (25-29.9 Kg/m2) or obesity (≥30 kg/m2). Data were gathered on sociodemographic characteristics, clinical variables (medication for anxiety/depression, Charlson Comorbidity Index, length of hospital stay), physical exercise and diet (International Physical Activity and Pardo Questionnaires), and HRQoL (EQ-5D-5L). The study included 98 patients with overweight (58.2% males) and 177 with obesity (52% males). In comparison to patients with obesity, those with overweight obtained better results for regular physical exercise (p = 0.007), healthy diet (p = 0.004), and "emotional eating" (p = 0.017). No between-group difference was found in HqoL scores. Patients with overweight and obesity differ in healthy dietary and physical exercise behaviors. Greater efforts are warranted to prevent an increase in the BMI of patients, paying special attention to their state of mind.
  • Publication
    Multidisciplinary Unit Improves Pregnancy Outcomes in Women with Rheumatic Diseases and Hereditary Thrombophilias: An Observational Study.
    (2021-04-03) Añón-Oñate, Isabel; Cáliz-Cáliz, Rafael; Rosa-Garrido, Carmen; Pérez-Galán, María José; Quirosa-Flores, Susana; Pancorbo-Hidalgo, Pedro L
    Rheumatic diseases (RD) and hereditary thrombophilias (HT) can be associated with high-risk pregnancies. This study describes obstetric outcomes after receiving medical care at a multidisciplinary consultation (MC) and compares adverse neonatal outcomes (ANOs) before and after medical care at an MC. This study is a retrospective observational study among pregnant women with RD and HT treated at an MC of a university hospital (southern Spain) from 2012 to 2018. Absolute risk reduction (ARR) and number needed to treat (NNT) were calculated. A total of 198 pregnancies were registered in 143 women (112 with RD, 31 with HT), with 191 (96.5%) pregnancies without ANOs and seven (3.5%) pregnancies with some ANOs (five miscarriages and two foetal deaths). Results previous to the MC showed 60.8% of women had more than one miscarriage, with 4.2% experiencing foetal death. MC reduced the ANO rate by AAR = 60.1% (95%CI: 51.6-68.7%). The NNT to avoid one miscarriage was 1.74 (95%CI: 1.5-2.1) and to avoid one foetal death NNT = 35.75 (95CI%: 15.2-90.9). A total of 84.8% of newborns and 93.2% of women did not experience any complication. As a conclusion, the follow-up of RD or HT pregnant women in the MC drastically reduced the risk of ANOs in this population with a previous high risk.
  • Publication
    Making the choice between bioelectrical impedance measures for body hydration status assessment.
    (2021-04-08) Davydov, Dmitry M; Boev, Andrey; Gorbunov, Stas
    Situational or persistent body fluid deficit (i.e., de- or hypo-hydration) is considered a significant health risk factor. Bioimpedance analysis (BIA) has been suggested as an alternative to less reliable subjective and biochemical indicators of hydration status. The present study aimed to compare various BIA models in the prediction of direct measures of body compartments associated with hydration/osmolality. Fish (n = 20) was selected as a biological model for physicochemically measuring proximate body compartments associated with hydration such as water, dissolved proteins, and non-osseous minerals as the references or criterion points. Whole-body and segmental/local impedance measures were used to investigate a pool of BIA models, which were compared by Akaike Information Criterion in their ability to accurately predict the body components. Statistical models showed that 'volumetric-based' BIA measures obtained in parallel, such as distance2/Rp, could be the best approach in predicting percent of body moisture, proteins, and minerals in the whole-body schema. However, serially-obtained BIA measures, such as the ratio of the reactance to resistance and the resistance adjusted for distance between electrodes, were the best fitting in predicting the compartments in the segmental schema. Validity of these results should be confirmed on humans before implementation in practice.
  • Publication
    Methylenetetrahydrofolate Reductase (MTHFR) Gene Polymorphism and Infant's Anthropometry at Birth.
    (2021-03-03) Aguilar-Lacasaña, Sofía; López-Flores, Inmaculada; González-Alzaga, Beatriz; Giménez-Asensio, María José; Carmona, F David; Hernández, Antonio F; López Gallego, María Felicidad; Romero-Molina, Desirée; Lacasaña, Marina
    Identification of causal factors that influence fetal growth and anthropometry at birth is of great importance as they provide information about increased risk of disease throughout life. The association between maternal genetic polymorphism MTHFR(677)C>T and anthropometry at birth has been widely studied because of its key role in the one-carbon cycle. MTHFR(677) CT and TT genotypes have been associated with a greater risk of low birth weight, especially in case of deficient intake of folic acid during pregnancy. This study aimed to analyze the association between the maternal MTHFR(677)C>T genetic polymorphism and anthropometry at birth in a population with adequate folate consumption. We included 694 mother-newborn pairs from a prospective population-based birth cohort in Spain, in the Genetics, Early life enviroNmental Exposures and Infant Development in Andalusia (GENEIDA) project. Women were genotyped for MTHFR(677)C>T SNP by Q-PCR using TaqMan© probes. Relevant maternal and newborn information was obtained from structured questionnaires and medical records. Results showed that maternal MTHFR(677)C>T genotype was associated with newborn anthropometry. Genotypes CT or CT/TT showed statistically significant associations with increased or decreased risk of large-for-gestational-age (LGA) or small-for-gestational-age (SGA) based on weight and height, depending on the newborn's sex, as well as with SGA in premature neonates. The relationships between this maternal genotype and anthropometry at birth remained despite an adequate maternal folate intake.
  • Publication
    Proteome Comparison Between Natural Desiccation-Tolerant Plants and Drought-Protected Caspicum annuum Plants by Microbacterium sp. 3J1.
    (2020-07-10) García-Fontana, Cristina; Vilchez, Juan Ignacio; Manzanera, Maximino
    Desiccation-tolerant plants are able to survive for extended periods of time in the absence of water. The molecular understanding of the mechanisms used by these plants to resist droughts can be of great value for improving drought tolerance in crops. This understanding is especially relevant in an environment that tends to increase the number and intensity of droughts. The combination of certain microorganisms with drought-sensitive plants can improve their tolerance to water scarcity. One of these bacteria is Microbacterium sp. 3J1, an actinobacteria able to protect pepper plants from drought. In this study, we supplemented drought-tolerant and drought-sensitive plant rhizospheres with Microbacterium sp. 3J1 and analyzed their proteomes under drought to investigate the plant-microbe interaction. We also compare this root proteome with the proteome found in desiccation-tolerant plants. In addition, we studied the proteome of Microbacterium sp. 3J1 subjected to drought to analyze its contribution to the plant-microbe interaction. We describe those mechanisms shared by desiccation-tolerant plants and sensitive plants protected by microorganisms focusing on protection against oxidative stress, and production of compatible solutes, plant hormones, and other more specific proteins.
  • Publication
    Predictive Model of the Risk of In-Hospital Mortality in Colorectal Cancer Surgery, Based on the Minimum Basic Data Set.
    (2020-06-12) García-Torrecillas, Juan Manuel; Olvera-Porcel, María Carmen; Ferrer-Márquez, Manuel; Rosa-Garrido, Carmen; Rodríguez-Barranco, Miguel; Lea-Pereira, María Carmen; Rubio-Gil, Francisco; Sánchez, María-José
    Various models have been proposed to predict mortality rates for hospital patients undergoing colorectal cancer surgery. However, none have been developed in Spain using clinical administrative databases and none are based exclusively on the variables available upon admission. Our study aim is to detect factors associated with in-hospital mortality in patients undergoing surgery for colorectal cancer and, on this basis, to generate a predictive mortality score. A population cohort for analysis was obtained as all hospital admissions for colorectal cancer during the period 2008-2014, according to the Spanish Minimum Basic Data Set. The main measure was actual and expected mortality after the application of the considered mathematical model. A logistic regression model and a mortality score were created, and internal validation was performed. 115,841 hospitalization episodes were studied. Of these, 80% were included in the training set. The variables associated with in-hospital mortality were age (OR: 1.06, 95%CI: 1.05-1.06), urgent admission (OR: 4.68, 95% CI: 4.36-5.02), pulmonary disease (OR: 1.43, 95%CI: 1.28-1.60), stroke (OR: 1.87, 95%CI: 1.53-2.29) and renal insufficiency (OR: 7.26, 95%CI: 6.65-7.94). The level of discrimination (area under the curve) was 0.83. This mortality model is the first to be based on administrative clinical databases and hospitalization episodes. The model achieves a moderate-high level of discrimination.
  • Publication
    Seroprevalence and epidemiology of hepatitis B and C viruses in pregnant women in Spain. Risk factors for vertical transmission.
    (2020-05-21) Ruiz-Extremera, Ángeles; Díaz-Alcázar, María Del Mar; Muñoz-Gámez, José Antonio; Cabrera-Lafuente, Marta; Martín, Estefanía; Arias-Llorente, Rosa Patricia; Carretero, Pilar; Gallo-Vallejo, José Luis; Romero-Narbona, Francisca; Salmerón-Ruiz, M A; Alonso-Diaz, Clara; Maese-Heredia, Rafael; Cerrillos, Lucas; Fernández-Alonso, Ana María; Camarena, Carmen; Aguayo, Josefa; Sánchez-Forte, Miguel; Rodríguez-Maresca, Manuel; Pérez-Rivilla, Alfredo; Quiles-Pérez, Rosa; Muñoz de Rueda, Paloma; Expósito-Ruiz, Manuela; García, Federico; García, Fernando; Salmerón, Javier
    Worldwide, measures are being implemented to eradicate hepatitis B (HBV) and C (HCV) viruses, which can be transmitted from the mother during childbirth. This study aims to determine the prevalence of HBV and HCV in pregnant women in Spain, focusing on country of origin, epidemiological factors and risk of vertical transmission (VT). Multicentre open-cohort study performed during 2015. HBV prevalence was determined in 21870 pregnant women and HCV prevalence in 7659 pregnant women. Epidemiological and risk factors for VT were analysed in positive women and differences between HBV and HCV cases were studied. HBV prevalence was 0.42% (91/21870) and HCV prevalence was 0.26% (20/7659). Of the women with HBV, 65.7% (44/67) were migrants. The HBV transmission route to the mother was unknown in 40.3% of cases (27/67) and VT in 31.3% (21/67). Among risk factors for VT, 67.7% (42/62) of the women had viraemia and 14.5% (9/62) tested HBeAg-positive. All of the neonates born to HBV-positive mothers received immunoprophylaxis, and none contracted infection by VT. In 80% (16/20) of the women with HCV, the transmission route was parenteral, and nine were intravenous drug users. Viraemia was present in 40% (8/20) of the women and 10% (2/20) were HIV-coinfected. No children were infected. Women with HCV were less likely than women with HBV to breastfeed their child (65% vs. 86%). The prevalences obtained in our study of pregnant women are lower than those previously documented for the general population. Among the women with HBV, the majority were migrants and had a maternal family history of infection, while among those with HCV, the most common factor was intravenous drug use. Despite the risk factors observed for VT, none of the children were infected. Proper immunoprophylaxis is essential to prevent VT in children born to HBV-positive women.
  • Publication
    Development and Validation of the EspaiJove.net Mental Health Literacy (EMHL) Test for Spanish Adolescents.
    (2019-12-20) Castellvi, Pere; Casañas, Rocío; Arfuch, Victoria-Mailen; Gil Moreno, Juan José; Torres Torres, María; García-Forero, Carlos; Ruiz-Castañeda, Dyanne; Alonso, Jordi; Lalucat-Jo, Lluís
    There is evidence of the effectiveness of implementing mental health literacy (MHL) programs. However, there are substantial limitations in the instruments available for measuring MHL. This study aimed to develop and validate the EspaiJove.net MHL test (EMHL) for Spanish adolescents by assessing its psychometric properties. The development of the EMHL test was conducted using item pool generation and a pilot study. A convenience sample of students aged 13-15 years (n = 355) participated in the validity study. Reliability was assessed for internal consistency and via test-retest. Convergent validity was evaluated by comparing the effect sizes among known groups with different levels of mental health knowledge, the correlation with mental health-related instruments, and the item discrimination index. A final version of a 35-item EMHL test was obtained with two parts: (i) a binary choice format (yes/no) for the identification of mental disorders; (ii) a multiple choice question with four possible answer options. Internal consistency was acceptable in the first part (Cronbach's alpha = 0.744; Guttman's lambda 2 = 0.773) and almost acceptable in the second part (Cronbach's alpha = 0.615; Guttman's lambda 2 = 0.643). The test-retest evaluation supported the stability of the test (first part, ICC = 0.578; second part, ICC = 0.422). No ceiling and floor effects were found. The EMHL test scores discriminated between known groups with different levels of mental health knowledge and it is associated with several-related constructs of MHL. Conclusions: The EMHL test is a relevant measure for assessing MHL in adolescents into Spanish context with acceptable validity and stability.