Instituto de Investigación Biomédica de Málaga - Plataforma Bionand (IBIMA)

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  • Publication
    Standardization of molecular monitoring of CML: results and recommendations from the European treatment and outcome study.
    (2022-05-25) White, Helen E; Salmon, Matthew; Albano, Francesco; Andersen, Christina Søs Auður; Balabanov, Stefan; Balatzenko, Gueorgui; Barbany, Gisela; Cayuela, Jean-Michel; Cerveira, Nuno; Cochaux, Pascale; Colomer, Dolors; Coriu, Daniel; Diamond, Joana; Dietz, Christian; Dulucq, Stéphanie; Engvall, Marie; Franke, Georg N; Gineikiene-Valentine, Egle; Gniot, Michal; Gómez-Casares, María Teresa; Gottardi, Enrico; Hayden, Chloe; Hayette, Sandrine; Hedblom, Andreas; Ilea, Anca; Izzo, Barbara; Jiménez-Velasco, Antonio; Jurcek, Tomas; Kairisto, Veli; Langabeer, Stephen E; Lion, Thomas; Meggyesi, Nora; Mešanović, Semir; Mihok, Luboslav; Mitterbauer-Hohendanner, Gerlinde; Moeckel, Sylvia; Naumann, Nicole; Nibourel, Olivier; Oppliger Leibundgut, Elisabeth; Panayiotidis, Panayiotis; Podgornik, Helena; Pott, Christiane; Rapado, Inmaculada; Rose, Susan J; Schäfer, Vivien; Touloumenidou, Tasoula; Veigaard, Christopher; Venniker-Punt, Bianca; Venturi, Claudia; Vigneri, Paolo; Vorkinn, Ingvild; Wilkinson, Elizabeth; Zadro, Renata; Zawada, Magdalena; Zizkova, Hana; Müller, Martin C; Saussele, Susanne; Ernst, Thomas; Machova Polakova, Katerina; Hochhaus, Andreas; Cross, Nicholas C P
    Standardized monitoring of BCR::ABL1 mRNA levels is essential for the management of chronic myeloid leukemia (CML) patients. From 2016 to 2021 the European Treatment and Outcome Study for CML (EUTOS) explored the use of secondary, lyophilized cell-based BCR::ABL1 reference panels traceable to the World Health Organization primary reference material to standardize and validate local laboratory tests. Panels were used to assign and validate conversion factors (CFs) to the International Scale and assess the ability of laboratories to assess deep molecular response (DMR). The study also explored aspects of internal quality control. The percentage of EUTOS reference laboratories (n = 50) with CFs validated as optimal or satisfactory increased from 67.5% to 97.6% and 36.4% to 91.7% for ABL1 and GUSB, respectively, during the study period and 98% of laboratories were able to detect MR4.5 in most samples. Laboratories with unvalidated CFs had a higher coefficient of variation for BCR::ABL1IS and some laboratories had a limit of blank greater than zero which could affect the accurate reporting of DMR. Our study indicates that secondary reference panels can be used effectively to obtain and validate CFs in a manner equivalent to sample exchange and can also be used to monitor additional aspects of quality assurance.
  • Publication
    Serum vascular endothelial growth factor b and metabolic syndrome incidence in the population based cohort study.
    (2022-08-20) Lago-Sampedro, Ana; Lhamyani, Said; Valdés, Sergio; Colomo, Natalia; Maldonado-Araque, Cristina; González-Molero, Inmaculada; Doulatram-Gamgaram, Viyey; Delgado, Elias; Chaves, Felipe J; Castaño, Luis; Calle-Pascual, Alfonso; Franch-Nadal, Josep; Rojo-Martínez, Gemma; García-Serrano, Sara; García-Escobar, Eva
    Although vascular endothelial growth factor b (VEGFb) might have an impact on the development of obesity, diabetes and related disorders, the possible relationship between VEGFb serum levels and the incidence of these metabolic complications in humans is still unknown. The aim of our study was to evaluate the association between VEGFb serum levels and the new-onset of metabolic syndrome (MS) and its components in the Spanish adult population after 7.5 years of follow-up. A total of 908 subjects from the cohort study without MS at cross-sectional stage according to International Diabetes Federation (IDF) or Adult Treatment Panel III (ATP-III) criteria were included. Additionally, five sub-populations were grouped according to the absence of each MS component at baseline. Socio-demographic, anthropometric and clinical data were recorded. The Short Form of International Physical Activity Questionnaire (SF-IPAQ) was used to estimate physical activity. A fasting blood extraction and an oral glucose tolerance test were performed. Serum determinations of glucose, lipids, hsCRP and insulin were made. VEGFb levels were determined and categorized according to the 75th percentile of the variable. New cases of MS and its components were defined according to ATPIII and IDF criteria. A total of 181 or 146 people developed MS defined by IDF or ATP-III criteria respectively. Serum triglyceride levels, hs-CRP and systolic blood pressure at the baseline study were significantly different according to the VEGFb categories. Adjusted logistic regression analysis showed that the likelihood of developing MS and abdominal obesity was statistically reduced in subjects included in the higher VEGFb category. Low serum levels of VEGFb may be considered as early indicators of incident MS and abdominal obesity in the Spanish adult population free of MS, independently of other important predictor variables.
  • Publication
    The emergent role of mitochondrial RNA modifications in metabolic alterations.
    (2022-07-25) Boughanem, Hatim; Böttcher, Yvonne; Tomé-Carneiro, João; López de Las Hazas, María-Carmen; Dávalos, Alberto; Cayir, Akin; Macias-González, Manuel
    Mitochondrial epitranscriptomics refers to the modifications occurring in all the different RNA types of mitochondria. Although the number of mitochondrial RNA modifications is less than those in cytoplasm, substantial evidence indicates that they play a critical role in accurate protein synthesis. Recent evidence supported those modifications in mitochondrial RNAs also have crucial implications in mitochondrial-related diseases. In the light of current knowledge about the involvement, the association between mitochondrial RNA modifications and diseases arises from studies focusing on mutations in both mitochondrial and nuclear DNA genes encoding enzymes involved in such modifications. Here, we review the current evidence available for mitochondrial RNA modifications and their role in metabolic disorders, and we also explore the possibility of using them as promising targets for prevention and early detection. Finally, we discuss future directions of mitochondrial epitranscriptomics in these metabolic alterations, and how these RNA modifications may offer a new diagnostic and theragnostic avenue for preventive purposes. This article is categorized under: RNA Processing > RNA Editing and Modification.
  • Publication
    2-(Fluoromethoxy)-4'-(S-methanesulfonimidoyl)-1,1'-biphenyl (UCM-1306), an Orally Bioavailable Positive Allosteric Modulator of the Human Dopamine D1 Receptor for Parkinson's Disease.
    (2022-08-31) García-Cárceles, Javier; Vázquez-Villa, Henar; Brea, José; Ladron de Guevara-Miranda, David; Cincilla, Giovanni; Sánchez-Martínez, Melchor; Sánchez-Merino, Anabel; Algar, Sergio; Teresa de Los Frailes, María; Roberts, Richard S; Ballesteros, Juan A; Rodríguez de Fonseca, Fernando; Benhamú, Bellinda; Loza, María I; López-Rodríguez, María L
    Tolerance development caused by dopamine replacement with l-DOPA and therapeutic drawbacks upon activation of dopaminergic receptors with orthosteric agonists reveal a significant unmet need for safe and effective treatment of Parkinson's disease. In search for selective modulators of the D1 receptor, the screening of a chemical library and subsequent medicinal chemistry program around an identified hit resulted in new synthetic compound 26 [UCM-1306, 2-(fluoromethoxy)-4'-(S-methanesulfonimidoyl)-1,1'-biphenyl] that increases the dopamine maximal effect in a dose-dependent manner in human and mouse D1 receptors, is inactive in the absence of dopamine, modulates dopamine affinity for the receptor, exhibits subtype selectivity, and displays low binding competition with orthosteric ligands. The new allosteric modulator potentiates cocaine-induced locomotion and enhances l-DOPA recovery of decreased locomotor activity in reserpinized mice after oral administration. The behavior of compound 26 supports the interest of a positive allosteric modulator of the D1 receptor as a promising therapeutic approach for Parkinson's disease.
  • Publication
    Discovery of V-0219: A Small-Molecule Positive Allosteric Modulator of the Glucagon-Like Peptide-1 Receptor toward Oral Treatment for "Diabesity".
    (2022-03-29) Decara, Juan M; Vázquez-Villa, Henar; Brea, José; Alonso, Mónica; Srivastava, Raj Kamal; Orio, Laura; Alén, Francisco; Suárez, Juan; Baixeras, Elena; García-Cárceles, Javier; Escobar-Peña, Andrea; Lutz, Beat; Rodríguez, Ramón; Codesido, Eva; Garcia-Ladona, F Javier; Bennett, Teresa A; Ballesteros, Juan A; Cruces, Jacobo; Loza, María I; Benhamú, Bellinda; Rodríguez de Fonseca, Fernando; López-Rodríguez, María L
    Peptidic agonists of the glucagon-like peptide-1 receptor (GLP-1R) have gained a prominent role in the therapy of type-2 diabetes and are being considered for reducing food intake in obesity. Potential advantages of small molecules acting as positive allosteric modulators (PAMs) of GLP-1R, including oral administration and reduced unwanted effects, could improve the utility of this class of drugs. Here, we describe the discovery of compound 9 (4-{[1-({3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl}methyl)piperidin-3-yl]methyl}morpholine, V-0219) that exhibits enhanced efficacy of GLP-1R stimulation, subnanomolar potency in the potentiation of insulin secretion, and no significant off-target activities. The identified GLP-1R PAM shows a remarkable in vivo activity, reducing food intake and improving glucose handling in normal and diabetic rodents. Enantioselective synthesis revealed oral efficacy for (S)-9 in animal models. Compound 9 behavior bolsters the interest of a small-molecule PAM of GLP-1R as a promising therapeutic approach for the increasingly prevalent obesity-associated diabetes.
  • Publication
    Shared Clavulanate and Tazobactam Antigenic Determinants Activate T-Cells from Hypersensitive Patients.
    (2022-09-22) Ariza, Adriana; Jaruthamsophon, Kanoot; Meng, Xiaoli; Labella, Marina; Adair, Kareena; Tailor, Arun; Sukasem, Chonlaphat; Whitaker, Paul; Peckham, Daniel; Pirmohamed, Munir; Torres, María José; Naisbitt, Dean John
    β-Lactamase inhibitors such as clavulanic acid and tazobactam were developed to overcome β-lactam antibiotic resistance. Hypersensitivity reactions to these drugs have not been studied in detail, and the antigenic determinants that activate T-cells have not been defined. The objectives of this study were to (i) characterize clavulanate- and tazobactam-responsive T-cells from hypersensitive patients, (ii) explore clavulanate and tazobactam T-cell crossreactivity, and (iii) define the antigenic determinants that contribute to T-cell reactivity. Antigen specificity, pathways of T-cell activation, and crossreactivity with clavulanate- and tazobactam-specific T-cell clones were assessed by proliferation and cytokine release assays. Antigenic determinants were analyzed by mass spectrometry-based proteomics methods. Clavulanate- and tazobactam-responsive CD4+ T-cell clones were stimulated to proliferate and secrete IFN-γ in an MHC class II-restricted and dose-dependent manner. T-cell activation with clavulanate- and tazobactam was dependent on antigen presenting cells because their fixation prevented the T-cell response. Strong crossreactivity was observed between clavulanate- and tazobactam-T-cells; however, neither drug activated β-lactam antibiotic-responsive T-cells. Mass spectrometric analysis revealed that both compounds form multiple antigenic determinants with lysine residues on proteins, including an overlapping aldehyde and hydrated aldehyde adduct with mass additions of 70 and 88 Da, respectively. Collectively, these data show that although clavulanate and tazobactam are structurally distinct, the antigenic determinants formed by both drugs overlap, which explains the observed T-cell cross-reactivity.
  • Publication
    Dietary diversity and depression: cross-sectional and longitudinal analyses in Spanish adult population with metabolic syndrome. Findings from PREDIMED-Plus trial.
    (2022-07-19) Cano-Ibáñez, Naomi; Serra-Majem, Lluis; Martín-Peláez, Sandra; Martínez-González, Miguel Ángel; Salas-Salvadó, Jordi; Corella, Dolores; Lassale, Camille; Martínez, Jose Alfredo; Alonso-Gómez, Ángel M; Wärnberg, Julia; Vioque, Jesús; Romaguera, Dora; López-Miranda, José; Estruch, Ramon; Gómez-Pérez, Ana María; Lapetra, José; Fernández-Aranda, Fernando; Bueno-Cavanillas, Aurora; Tur, Josep A; Cubelos, Naiara; Pintó, Xavier; Gaforio, José Juan; Matía-Martín, Pilar; Vidal, Josep; Calderón, Cristina; Daimiel, Lidia; Ros, Emilio; Gea, Alfredo; Babio, Nancy; Gimenez-Alba, Ignacio Manuel; Zomeño-Fajardo, María Dolores; Abete, Itziar; Tojal Sierra, Lucas; Romero-Galisteo, Rita P; García de la Hera, Manoli; Martín-Padillo, Marian; García-Ríos, Antonio; Casas, Rosa M; Fernández-García, J C; Santos-Lozano, José Manuel; Toledo, Estefanía; Becerra-Tomas, Nerea; Sorli, Jose V; Schröder, Helmut; Zulet, María A; Sorto-Sánchez, Carolina; Diez-Espino, Javier; Gómez-Martínez, Carlos; Fitó, Montse; Sánchez-Villegas, Almudena
    To examine the cross-sectional and longitudinal (2-year follow-up) associations between dietary diversity (DD) and depressive symptoms. An energy-adjusted dietary diversity score (DDS) was assessed using a validated FFQ and was categorised into quartiles (Q). The variety in each food group was classified into four categories of diversity (C). Depressive symptoms were assessed with Beck Depression Inventory-II (Beck II) questionnaire and depression cases defined as physician-diagnosed or Beck II >= 18. Linear and logistic regression models were used. Spanish older adults with metabolic syndrome (MetS). A total of 6625 adults aged 55-75 years from the PREDIMED-Plus study with overweight or obesity and MetS. Total DDS was inversely and statistically significantly associated with depression in the cross-sectional analysis conducted; OR Q4 v. Q1 = 0·76 (95 % CI (0·64, 0·90)). This was driven by high diversity compared to low diversity (C3 v. C1) of vegetables (OR = 0·75, 95 % CI (0·57, 0·93)), cereals (OR = 0·72 (95 % CI (0·56, 0·94)) and proteins (OR = 0·27, 95 % CI (0·11, 0·62)). In the longitudinal analysis, there was no significant association between the baseline DDS and changes in depressive symptoms after 2 years of follow-up, except for DD in vegetables C4 v. C1 = (β = 0·70, 95 % CI (0·05, 1·35)). According to our results, DD is inversely associated with depressive symptoms, but eating more diverse does not seem to reduce the risk of future depression. Additional longitudinal studies (with longer follow-up) are needed to confirm these findings.
  • Publication
    Utility of PHQ-2, PHQ-8 and PHQ-9 for detecting major depression in primary health care: a validation study in Spain.
    (2022-10-19) Gómez-Gómez, Irene; Benítez, Isabel; Bellón, Juan; Moreno-Peral, Patricia; Oliván-Blázquez, Bárbara; Clavería, Ana; Zabaleta-Del-Olmo, Edurne; Llobera, Joan; Serrano-Ripoll, Maria J; Tamayo-Morales, Olaya; Motrico, Emma
    Primary health care (PHC) professionals may play a crucial role in improving early diagnosis of depressive disorders. However, only 50% of cases are detected in PHC. The most widely used screening instrument for major depression is the Patient Health Questionnaire (PHQ), including the two-, eight- and nine-item versions. Surprisingly, there is neither enough evidence about the validity of PHQ in PHC patients in Spain nor indications about how to interpret the total scores. This study aimed to gather validity evidence to support the use of the three PHQ versions to screen for major depression in PHC in Spain. Additionally, the present study provided information for helping professionals to choose the best PHQ version according to the context. The sample was composed of 2579 participants from 22 Spanish PHC centers participating in the EIRA-3 study. The reliability and validity of the three PHQ versions for Spanish PHC patients were assessed based on responses to the questionnaire. The PHQ-8 and PHQ-9 showed high internal consistency. The results obtained confirm the theoretically expected relationship between PHQ results and anxiety, social support and health-related QoL. A single-factor solution was confirmed. Regarding to the level of agreement with the CIDI interview (used as the criterion), our results indicate that the PHQ has a good discrimination power. The optimal cut-off values were: ⩾2 for PHQ-2, ⩾7 for PHQ-8 and ⩾8 for PHQ-9. PHQ is a good and valuable tool for detecting major depression in PHC patients in Spain.
  • Publication
    The Mediterranean diet and physical activity: better together than apart for the prevention of premature mortality.
    (2021-08-31) Hershey, Maria Soledad; Martínez-González, Miguel Ángel; Álvarez-Álvarez, Ismael; Martínez Hernández, José Alfredo; Ruiz-Canela, Miguel
    Diet and physical activity (PA) have been studied extensively in epidemiology as single or combined lifestyle factors; however, their interaction has not been studied thoroughly. Studying potential synergisms between lifestyle components with a comprehensive interaction analysis, including additive measures of interaction, provides key insights into the nature of their joint effect and helps target interventions more effectively. First, a comprehensive review was conducted to assess the potential research gap regarding reported interaction analyses conducted in studies assessing the Mediterranean diet (MedDiet) in combination with PA on all-cause mortality. Thereafter, we prospectively assessed the joint association of the MedDiet with PA on all-cause mortality in the Seguimiento Universidad de Navarra (SUN) cohort, followed by both multiplicative and additive interaction analyses. The conjoint effect of low adherence to the MedDiet and low PA observed an increased risk greater than the individual risk factors, suggesting a potential additive interaction or synergism between both exposures, with relative risk due to interaction (RERI) and (95 % confidence interval (95 % CI)) = 0·46 (–0·83 to 1·75) and attributable proportion (95 % CI) due to interaction of 36 % (–0·62, 1·34). No multiplicative interaction was detected. Studying interactions between lifestyle factors, such as the MedDiet and PA, is particularly relevant given the current research gaps in studying the complexities of combined aspects of lifestyle in comparison with isolated behaviours. Our findings underline the important public health message of adhering to both the MedDiet and PA for the prevention of premature mortality.
  • Publication
    Form and function of the mantle edge in Protobranchia (Mollusca: Bivalvia).
    (2022-06-28) Salas, Carmen; Bueno-Pérez, Juan de Dios; López-Téllez, Juan Félix; Checa, Antonio G
    We analyzed, by optical and transmission electron microscopy, the morphology and function of the mantle edge, including the formation of the periostracum, of ten species of protobranchs. Five species from the order Nuculida, four species from the order Nuculanida and one species from the order Solemyida were studied. A second outer fold, which seems to function as a template for the internal marginal crenulations of the valves, is present in the crenulated species of Nucula. The minute non-crenulated Ennucula aegeensis shows the glandular basal cells displaced toward the periostracal groove, resembling a minute additional fold between the outer and middle folds. Intense secretion of glycocalyx, together with active uptake of particles, have been observed in the inner epithelium of the middle mantle fold and the whole epithelium of the inner mantle fold in all the studied species. Contrary to the rest of the bivalves, all the protobranchs analyzed have two basal cells involved in the formation of the external nanometric pellicle of the periostracum, a character that would support the monophyly of protobranchs. A three-layered pattern is the general rule for the periostracum in protobranchs, like for other bivalves. The presence of pouches of translucent layer inside the tanned dark layer under periostracal folds is characteristic of the species with a folded periostracum; its function is unclear but could give flexibility to the periostracum. The non-nacreous internal shell layer and the presence of translucent pouches under periostracal folds in Sarepta speciosa resemble those found in nuculanids. However, the free periostracum is rather similar to those of N. hanleyi and E. aegeensis, with a continuous vesicular layer. All the latter supports the inclusion of Sarepta in the order Nuculanida but could indicate either a basal lineage or that the translucent vesicular layer is an adaptive trait.
  • Publication
    EEG abnormalities and clinical phenotypes in pre-school children with autism spectrum disorder.
    (2022-03-15) Romero-González, Marina; Navas-Sánchez, Patricia; Marín-Gámez, Ester; Barbancho-Fernández, Miguel Angel; Fernández-Sánchez, Victoria Eugenia; Lara-Muñoz, José Pablo; Guzmán-Parra, José
    Abnormalities on electroencephalography (EEG) results have been reported in a high percentage of children with Autism Spectrum Disorder (ASD). The purpose of this study was to explore the prevalence of EEG abnormalities in a clinical population of pre-school children with Autism Spectrum Disorder and the differences in terms of the following phenotypic characteristics: adaptive behavior, executive functioning, severity of Autism Spectrum Disorder core symptoms, and comorbidity symptoms. A cross-sectional analysis of 69 children who attended the Autism Spectrum Disorder early diagnosis program with electroencephalography and clinical diagnosis was performed. A battery of questionnaires was also made to parents to evaluate emotions, behavior, and functional skills for daily living. Out of 69 pre-school children with Autism Spectrum Disorder, twenty nine (42%) had abnormalities in electroencephalography results. The group with abnormal epileptiform electroencephalography exhibited more impairment in executive functioning and social-relationship coexisting symptoms. The presence of an abnormal epileptiform electroencephalography in pre-school children with ASD already suggests a worse development in clinical features.
  • Publication
    Standards for practical intravenous rapid drug desensitization & delabeling: A WAO committee statement
    (Elsevier, 2022-05-31) Madrigal-Burgaleta, Ricardo; [Madrigal-Burgaleta, Ricardo] Ramon & Cajal Univ Hosp, Madrid, Spain; [Madrigal-Burgaleta, Ricardo] St Bartholomews Hosp, Resp Dept, Allergy & Severe Asthma Serv, Barts Hlth NHS Trust, 4th Floor,King George 5 Bldg, London EC1A 7BE, England
    Drug hypersensitivity reactions (DHRs) to intravenous drugs can be severe , might leave pa-tients and doctors in a difficult position where an essential treatment or intervention has to be suspended. Even if virtually any intravenous medication can potentially trigger a life-threatening DHR, chemotherapeutics, biologics , antibiotics are amongst the intravenous drugs most frequently involved in these reactions. Admittedly, suspending such treatments may negatively impact the survival outcomes or the quality of life of affected patients. Delabeling pathways and rapid drug desensitization (RDD) can help reactive patients stay on first -choice therapies instead of turning to less efficacious, less cost-effective, or more toxic alternatives. However, these are high-complexity and high-risk techniques, which usually need expert teams and allergy-specific techniques (skin testing, in vitro testing, drug provocation testing) to ensure safety, an accurate diagnosis, and personalized management. Unfortunately, there are significant inequalities within and among countries in access to allergy departments with the necessary expertise and resources to offer these techniques and tackle these DHRs optimally. The main objective of this consensus document is to create a great benefit for patients worldwide by aiding allergists to expand the scope of their practice and support them with evidence, data, and experience from leading groups from around the globe. This statement of the Drug Hypersensitivity Committee of the World Allergy Organization (WAO) aims to be a comprehensive practical guide on the technical aspects of implementing acute-onset intravenous hypersensitivity delabeling and RDD for a wide range of drugs. Thus, the manuscript does not only focus on clinical pathways. Instead, it also provides guidance on topics usually left unaddressed, namely, internal validation, continuous quality improvement, creating a healthy multidisciplinary environment, and redesigning care (including a specific supplemental section on a real-life example of how to design a dedicated space that can combine basic and complex diagnostic and therapeutic techniques in allergy).
  • Publication
    Humoral Response After SARS-CoV-2 Vaccination in Kidney Transplant Recipients: Role of Immunosuppression Therapy.
    (2022-10-03) López, Verónica; Polo, Carolina; Schuldt, Ruben; Vázquez, Teresa; Gutiérrez-Vílchez, Elena; Moliz, Candela; Hernández, Domingo
    Messenger RNA vaccination against COVID-19 has been shown to produce an immune response with sufficient efficacy to prevent natural infection in immunocompetent recipients. However, the response in kidney transplant recipients is low. We aimed to evaluate the specific humoral response to SARS-CoV-2 after vaccination in a population of kidney transplant recipients and assess the main factors associated with a lack of response. We undertook a prospective study of 105 kidney transplant recipients and 11 recipients of a combined kidney-pancreas transplant. We analyzed immunoglobulin G and immunoglobulin M antibodies after the patients received their second and third doses of the messenger RNA 1273 (Moderna) or BNT162b1 (BionTECH-Pfizer) vaccinations between February and November 2021. Mean (SD) age of the 116 patients was 50 (16) years, and 65% were men. They had their transplants for 40 months (IQR, 15-123 months), with 14% undergoing retransplant and 11% sensitized. The maintenance immunosuppression regimen was steroids + tacrolimus + mycophenolate (MMF) in 68% of the patients and any combination with mammalian target of rapamycin inhibitor (mTORi) in 28%. A humoral response developed in 40% of the patients 6 weeks (IQR, 4-10 weeks) after receiving the second dose of the vaccine. Of the 67 patients with no response to the second dose, 51 had an analysis of the humoral response after the third dose, which was positive in 16 (31%). A total of 80% received the Moderna vaccine and 20% the BionTECH-Pfizer. No patient experienced major adverse effects after the vaccination. Factors associated with a lack of humoral response to the vaccine were recipient age (odds ratio [OR], 1.02; 95% CI, 1.001-1.05; P = .04), diabetes (OR, 2.8; 95% CI, 1.2-6.9; P = .02), and treatment with MMF (OR, 2.6; 95% CI, 1.08-6.8; P = .03). Treatment with mTORi was associated with a better response to vaccination (OR, 0.3; 95% CI, 0.1-0.9; P = .04). The humoral response to the COVID-19 vaccine in kidney transplant recipients is poor. Factors related with this lack of immunity are recipient age and diabetes, plus MMF therapy, whereas mTORi therapy was associated with a better response to vaccination.
  • Publication
    Spanish validation of the national league for nursing questionnaires for clinical simulation
    (Elsevier science inc, 2022-03-11) Roman-Cereto, Montserrat; Marti-Garcia, Celia; Garcia-Mayor, Silvia; Kaknani-Uttumchandani, Shakira; Garcia-Gamez, Marina; Fernandez Ordonez, Eloisa; Leon-Campos, Alvaro; Gutierrez-Rodriguez, Laura; Miguel Morales-Asencio, Jose; [Roman-Cereto, Montserrat] Univ Malaga, Fac Ciencias Salud, Dist Sanitario Malaga Guadalhorce, Dept Enfermeria, Malaga, Spain; [Marti-Garcia, Celia] Univ Malaga, Fac Ciencias Salud, Dept Enfermeria, Malaga, Spain; [Garcia-Gamez, Marina] Univ Malaga, Fac Ciencias Salud, Dept Enfermeria, Malaga, Spain; [Fernandez Ordonez, Eloisa] Univ Malaga, Fac Ciencias Salud, Dept Enfermeria, Malaga, Spain; [Gutierrez-Rodriguez, Laura] Univ Malaga, Fac Ciencias Salud, Dept Enfermeria, Malaga, Spain; [Garcia-Mayor, Silvia] Univ Malaga, Fac Ciencias Salud, Inst Invest Biomed Malaga IBIMA, Dept Enfermeria, Malaga, Spain; [Kaknani-Uttumchandani, Shakira] Univ Malaga, Fac Ciencias Salud, Inst Invest Biomed Malaga IBIMA, Dept Enfermeria, Malaga, Spain; [Leon-Campos, Alvaro] Univ Malaga, Fac Ciencias Salud, Inst Invest Biomed Malaga IBIMA, Dept Enfermeria, Malaga, Spain; [Miguel Morales-Asencio, Jose] Univ Malaga, Fac Ciencias Salud, Inst Invest Biomed Malaga IBIMA, Dept Enfermeria, Malaga, Spain; University of Malaga
    Introduction: Learning by clinical simulation enables students to experience the nuances often encountered in clinical settings before experiencing actual real-world patient scenarios. Valid and reliable assessment tools are required to measure clinical competence. The aim of this study was to validate the National League for Nursing satisfaction instruments for its use in the Spanish context.Methods: Psychometric and cultural adaptation study. Student Satisfaction and Self-Confidence in Learning Scale, the Simulation Design Scale and the Educational Practices Questionnaire were adapted culturally, and their psychometric properties were tested empirically.Results: Fourth-year undergraduate nursing students participated in the study (n = 173). The Cronbach's alpha scores obtained ranged from 0.90 to 0.95. Confirmatory factor analysis revealed adequate goodness of fit values (RMSEA: 0.04 to 0.08).Conclusions: The Spanish-language version of the National League of Nursing instruments obtains satisfactory results. Further study is needed to determine the factorial invariance and whether any modifications in the instruments are needed. (C) 2021 The Authors. Published by Elsevier Inc. on behalf of Organization for Associate Degree Nursing.
  • Publication
    Satellite glia of the adult dorsal root ganglia harbor stem cells that yield glia under physiological conditions and neurons in response to injury.
    (2022) Maniglier, Madlyne; Vidal, Marie; Bachelin, Corinne; Deboux, Cyrille; Chazot, Jérémy; Garcia-Diaz, Beatriz; Baron-Van Evercooren, Anne
    The presence of putative stem/progenitor cells has been suggested in adult peripheral nervous system (PNS) tissue, including the dorsal root ganglion (DRG). To date, their identification and fate in pathophysiological conditions have not been addressed. Combining multiple in vitro and in vivo approaches, we identified the presence of stem cells in the adult DRG satellite glial population, and progenitors were present in the DRGs and sciatic nerve. Cell-specific transgenic mouse lines highlighted the proliferative potential of DRG stem cells and progenitors in vitro. DRG stem cells had gliogenic and neurogenic potentials, whereas progenitors were essentially gliogenic. Lineage tracing showed that, under physiological conditions, adult DRG stem cells maintained DRG homeostasis by supplying satellite glia. Under pathological conditions, adult DRG stem cells replaced DRG neurons lost to injury in addition of renewing the satellite glial pool. These novel findings open new avenues for development of therapeutic strategies targeting DRG stem cells for PNS disorders.
  • Publication
    Emerging noninvasive methylation biomarkers of cancer prognosis and drug response prediction.
    (2021-03-20) Oliver, Javier; Garcia-Aranda, Marilina; Chaves, Patricia; Alba, Emilio; Cobo-Dols, Manuel; Onieva, Juan Luis; Barragan, Isabel
    Cancer is the second leading cause of death worldwide being responsible for 9.6 million deaths in 2018. Epigenetic alterations are key in directing the aberrant expression of tumor-associated genes that drive cellular malignant transformation and cancer progression. Among epigenetic alterations, DNA methylation is the most deeply studied one in relation to environmental exposure. Tissue biopsies have traditionally been the main procedure by which a small sample of body tissue is excised to confirm cancer diagnosis or to indicate the primary site when cancer has spread. In contrast, the analysis of circulating tumor-derived material, or tumor circulome, by means of liquid biopsy of peripheral blood, urine, saliva or sputum is a noninvasive, fast and reproducible alternative to tissue biopsy. Recently, the assessment of epigenetic alterations such as DNA methylation and hydroxymethylation in circulating free DNA has been proved possible. These marks can be associated to prognosis and response to a variety of treatments including chemotherapy, hormonotherapy or immunotherapy. Epigenetic biomarkers may offer some advantages over RNA or genetic biomarkers given their stability in bodily fluids and their high tissue-specificity. While many challenges are still ahead, the unique advantages of these types of biomarkers is urging the scientific community to persevere in their clinical validation and integration into reliable prediction models. This review aims at recapitulating the emerging noninvasive DNA methylated biomarkers of importance for prediction of prognosis and drug response in cancer.
  • Publication
    User feedback and remote supervision for assisted living with mobile robots: A field study in long-term autonomy
    (Elsevier, 2022-09-01) Luperto, Matteo; Romeo, Marta; Monroy, Javier; Renoux, Jennifer; Vuono, Alessandro; Moreno, Francisco-Angel; Gonzalez-Jimenez, Javier; Basilico, Nicola; Borghese, N. Alberto; [Luperto, Matteo] Univ Milan, Dept Comp Sci, Appl Intelligent Syst Lab, Milan, Italy; [Vuono, Alessandro] Univ Milan, Dept Comp Sci, Appl Intelligent Syst Lab, Milan, Italy; [Basilico, Nicola] Univ Milan, Dept Comp Sci, Appl Intelligent Syst Lab, Milan, Italy; [Borghese, N. Alberto] Univ Milan, Dept Comp Sci, Appl Intelligent Syst Lab, Milan, Italy; [Romeo, Marta] Univ Manchester, Manchester, England; [Monroy, Javier] Univ Malaga, Dept Syst Engn & Automat, Machine Percept & Intelligent Robot Grp MAPIR, Malaga, Spain; [Moreno, Francisco-Angel] Univ Malaga, Dept Syst Engn & Automat, Machine Percept & Intelligent Robot Grp MAPIR, Malaga, Spain; [Gonzalez-Jimenez, Javier] Univ Malaga, Dept Syst Engn & Automat, Machine Percept & Intelligent Robot Grp MAPIR, Malaga, Spain; [Monroy, Javier] Univ Malaga, Inst Invest Biomed Malaga IBIMA BIONAND Platform, Malaga, Spain; [Moreno, Francisco-Angel] Univ Malaga, Inst Invest Biomed Malaga IBIMA BIONAND Platform, Malaga, Spain; [Gonzalez-Jimenez, Javier] Univ Malaga, Inst Invest Biomed Malaga IBIMA BIONAND Platform, Malaga, Spain; [Renoux, Jennifer] Orebro Univ, Machine Percept & Interact Lab, Orebro, Sweden; European Commission H2020-project MoveCare; Italian PON project SI-Robotics; project Essence
    In an ageing society, the at-home use of Socially Assistive Robots (SARs) could provide remote monitoring of their users' well-being, together with physical and psychological support. However, private home environments are particularly challenging for SARs, due to their unstructured and dynamic nature which often contributes to robots' failures. For this reason, even though several prototypes of SARs for elderly care have been developed, their commercialisation and wide-spread at-home use are yet to be effective. In this paper, we analyse how including the end users' feedback impacts the SARs reliability and acceptance. To do so, we introduce a Monitoring and Logging System (MLS) for remote supervision, which increases the explainability of SAR-based systems deployed in older adults' apartments, while also allowing the exchange of feedback between caregivers, technicians, and older adults. We then present an extensive field study showing how long-term deployment of autonomous SARs can be accomplished by relying on such a feedback loop to address any potential issue. To this end, we provide the results obtained in a 130-week long study where autonomous SARs were deployed in the apartments of 10 older adults, with the aim of possibly serving and assisting future practitioners, with the knowledge collected from this extensive experimental campaign, to fill the gap that currently exists for the widespread adoption of SARs. (c) 2022 Elsevier B.V. All rights reserved.
  • Publication
    Executive summary on the treatment of type 2 diabetes mellitus in elderly or frail individuals. 2022 update of the 2018 consensus document "Treatment of type 2 diabetes mellitus in the elderly".
    (2022-06-24) Gómez-Peralta, F; Carrasco-Sánchez, F J; Pérez, A; Escalada, J; Álvarez-Guisasola, F; Miranda-Fernández-Santos, C; Mediavilla-Bravo, J J; Gómez-Huelgas, R
    The population with type 2 DM (DM2) is highly heterogeneous, representing an important challenge for healthcare professionals. The therapeutic choice should be individualized, considering the functional status, frailty, the occurrence of comorbidities, and the preferences of patients and their caregivers. New evidence on the cardiovascular and renal protection of specific therapeutic groups and on the usefulness of new technologies for DM2 management, among other aspects, warrant an update of the consensus document on the DM2 in the elderly that was published in 2018.
  • Publication
    Doping and sports endocrinology: anabolic-androgenic steroids
    (Ediciones doyma s a, 2022-11-28) Garcia-Arnes, J. A.; Garcia-Casares, N.; [Garcia-Arnes, J. A.] Univ Malaga, Fac Med, Dept Farmacol, Malaga, Spain; [Garcia-Casares, N.] Univ Malaga, Fac Med, Dept Med, Malaga, Spain; [Garcia-Casares, N.] Univ Malaga, Ctr Invest Med Sanitarias CIMES, Malaga, Spain; [Garcia-Casares, N.] Inst Invest Biomed Malaga IBIMA, Malaga, Spain
    The use of anabolic steroids affects not only professional athletes but also the general population (bodybuilders, gym clients, and adolescents). In the first case, its use is prohibited and sanctioned by the World Anti-Doping Agency and Olympic committees. For the other users, it is difficult to establish its prevalence since many obtain the products via the Internet. The reasons for its use are varied and different forms of use and other types of users have been described. Among the side effects of steroid use, hypogonadism is the most frequent cause for endocrinological consultation. After a general introduction to doping, this review describes the historical background of anabolic-androgenic steroids, their classification, forms of use, phy-siological effects, adverse effects on different organs and systems, treatment of hypogonadism, as well as detection methods. (C) 2022 The Authors. Published by Elsevier Espana, S.L.U.
  • Publication
    [Persistent COVID-19 syndrome. A narrative review].
    (2021-11-15) López-Sampalo, A; Bernal-López, M R; Gómez-Huelgas, R
    As the coronavirus-2019 disease (COVID-19) pandemic, caused by the infection with severe acute respiratory syndrome (SARS-CoV-2) coronavirus type 2, has progressed, persistent COVID-19 syndrome is an increasingly recognized problem on which a significant volume of medical literature is developing. Symptoms may be persistent or appear, after an asymptomatic period, weeks or months after the initial infection. The clinical picture is as markedly heterogeneous and multisystemic as in the acute phase, so multidisciplinary management is required. In addition, their appearance is not related to the severity of the initial infection, so they can affect both mild patients, even asymptomatic, and seriously ill patients who have required hospitalization. Although it can affect people of any age, it is more common in middle-aged women. The sequelae can generate a high impact on the quality of life, and in the work and social environment. The objective of this paper is to review persistent COVID-19 syndrome, to know its clinical manifestations and the strategies for the management and follow-up of these patients.