Articles publicats en revistes (ISGlobal)

URI permanent per a aquesta col·leccióhttps://hdl.handle.net/2445/55586

Estadístiques

Examinar

Mostrant 1 - 20 de 1184

Penile Squamous Cell Carcinomas in Sub-Saharan Africa and Europe: Differential Etiopathogenesis
(MDPI, 2022-10-27) Manzotti, Carolina; Chulo, Laurina; López del Campo, Ricardo; Trias, Isabel; Pino Saladrigues, Marta del; Saude, Ofelia; Basílio, Iracema; Tchamo, Nelson; Lovane, Lucilia; Lorenzoni, Cesaltina; Fernandes, Fabiola; Saco, Adela; Rodrigo Calvo, María Teresa; Marimon, Lorena; Ismail, Mamudo R.; Carrilho, Carla; Ribera-Cortada, Inmaculada; Ordi i Majà, Jaume; Rakislova, Natalia
Penile squamous cell carcinomas (PSCC) are classified by the World Health Organization into two categories based on their relationship with the human papillomavirus (HPV): HPV-associated and HPV-independent. We compared a cohort of PSCC from Mozambique, a sub-Saharan country in southeast Africa with a high prevalence of HPV and HIV infection, and Spain, a country in southwestern Europe with a low prevalence of HPV and HIV, to study the distribution of the etiopathogenic categories of these tumors in both sites. A total of 79 PSCC were included in the study (28 from Mozambique and 51 from Spain). All cases underwent HPV-DNA polymerase chain reaction (PCR) testing, genotyping, and immunohistochemistry for p16 and p53. Any PSCC showing either p16 overexpression or HPV-DNA in PCR analysis was considered HPV-associated. Overall, 40/79 (50.6%) tumors were classified as HPV-associated and 39 (49.4%) as HPV-independent. The two sites showed marked differences: 25/28 (89.3%) tumors from Mozambique and only 15/51 (29.4%) from Spain were HPV-associated (p < 0.001). HPV16 was the most frequent HPV type identified in 64.0% (16/25) of the HPV-associated tumors from Mozambique, and 60.0% (9/15) from Spain (p = 0.8). On average, patients from Mozambique were almost two decades younger than those from Spain (mean age 50.9 ± 14.9 and 69.2 ± 13.3, respectively [p < 0.001]). In conclusion, significant etiopathogenic differences between PSCC in Mozambique and Spain were observed, with a remarkably high prevalence of HPV-associated tumors in Mozambique and a relatively low prevalence in Spain. These data may have important consequences for primary prevention of PSCC worldwide.
Association between type 2 diabetes and depressive symptoms after a 1-year follow-up in an older adult Mediterranean population
(Springer Nature, 2024-01-13) Baenas, Isabel; Camacho Barcia, Lucía; Granero, Roser; Razquin, Cristina; Corella Piquer, Dolores; Gómez Martínez, Carlos; Castañer Niño, Olga; Martínez, J. Alfredo; Alonso Gómez, Ángel M.; Wärnberg, Julia; Vioque, Jesús; Romaguera, Dora; López Miranda, José; Estruch Riba, Ramon; Tinahones, Francisco J.; Lapetra, José; Serra Majem, Lluís; Cano-Ibañez, Naomi; Tur Marí, Josep A. (Josep Antoni); Martín Sánchez, Vicente; Pintó Sala, Xavier; Gaforio, José Juan; Matía Martín, Pilar; Vidal i Cortada, Josep; Vázquez, Clotilde; Daimiel, Lidia; Ros Rahola, Emilio; Jiménez-Murcia, Susana; Dalsgaard, Søren; García Arellano, Ana; Babio, Nancy; Sorlí, José V.; Lassale, Camille; García de la Hera, Manuela; Gómez García, Enrique; Zulet, M. Angeles; Konieczna, Jadwiga; Martín-Peláez, Sandra; Tojal Sierra, Lucas; Basterra Gortari, F. Javier; Heras Delgado, Sara de las; Portolés, Olga; Muñoz Pérez, Miguel Ángel; Arenas Larriva, Antonio P.; Compañ Gabucio, Laura; Eguaras, Sonia; Shyam, Sangeetha; Fitó Colomer, Montserrat; Baños Rivera, Rosa María; Salas-Salvadó J; Fernández Aranda, Fernando
To examine the cross-sectional association between baseline depressive symptoms and the presence of type 2 diabetes (T2D), and its association with glycated hemoglobin (HbA1c) and other metabolic variables, and the prospective association of depressive symptoms and HbA1c after 1 year of follow-up. Methods: n = 6224 Mediterranean older adults with overweight/obesity and metabolic syndrome (48% females, mean age 64.9 ± 4.9 years) were evaluated in the framework of the PREDIMED-Plus study cohort. Depressive symptoms were assessed using the Beck Depression Inventory-II and HbA1c was used to measure metabolic control.Results: The presence of T2D increased the likelihood of higher levels of depressive symptoms (χ2 = 15.84, p = 0.001). Polynomial contrast revealed a positive linear relationship (χ2 = 13.49, p = 0.001), the higher the depressive symptoms levels, the higher the prevalence of T2D. Longitudinal analyses showed that the higher baseline depressive symptoms levels, the higher the likelihood of being within the HbA1c ≥ 7% at 1-year level (Wald-χ2 = 24.06, df = 3, p < .001, for the full adjusted model). Additionally, depressive levels at baseline and duration of T2D predicted higher HbA1c and body mass index, and lower physical activity and adherence to Mediterranean Diet at 1 year of follow-up. Conclusions: This study supports an association between T2D and the severity of depressive symptoms, suggesting a worse metabolic control from mild severity levels in the short-medium term, influenced by lifestyle habits related to diabetes care. Screening for depressive symptoms and a multidisciplinary integrative therapeutic approach should be ensured in patients with T2D
Alterations of the IKZF1-IKZF2 tandem in immune cells of schizophrenia patients regulate associated phenotypes
(BioMed Central, 2024-12-18) Ballasch, Iván; López Molina, Laura; Galán Ganga, Marcos; Sancho Balsells, Anna; Rodriguez Navarro, Irene; Borràs Pernas, Sara; Rabadán Lozano, M. Ángeles; Chen, Wanqi; Pastó Pellicer, Carlota; Flotta, Francesca; Maoyu, Wang; Fernández Irigoyen, Joaquín; Santamaría Martínez, Enrique; Aguilar, Ruth; Dobaño, Carlota, 1969-; Egri, Natalia; Hernández, Carla; Alfonso, Miqueu; Juan, Manel; Alberch i Vié, Jordi, 1959-; Toro Ruiz, Daniel del; Arranz, Belén; Canals i Coll, Josep M.; Giralt Torroella, Albert
Schizophrenia is a complex multifactorial disorder and increasing evidence suggests the involvement of immune dysregulations in its pathogenesis. We observed that IKZF1 and IKZF2, classic immune-related transcription factors (TFs), were both downregulated in patients’ peripheral blood mononuclear cells (PBMCs) but not in their brain. We generated a new mutant mouse model with a reduction in Ikzf1 and Ikzf2 to study the impact of those changes. Such mice developed deficits in the three dimensions (positive–negative-cognitive) of schizophrenia-like phenotypes associated with alterations in structural synaptic plasticity. We then studied the secretomes of cultured PBMCs obtained from patients and identified potentially secreted molecules, which depended on IKZF1 and IKZF2 mRNA levels, and that in turn have an impact on neural synchrony, structural synaptic plasticity and schizophrenia-like symptoms in in vivo and in vitro models. Our results point out that IKZF1-IKZF2-dependent immune signals negatively impact on essential neural circuits involved in schizophrenia.
Sociodemographic, clinical, and immunological factors associated with SARS-CoV-2 diagnosis and severe COVID-19 outcomes in people living with HIV: a retrospective cohort study.
(Elsevier B.V., 2021-10-13) Cortés, C.; Force, L.; Letang, Emilio; Vilaró, I.; Casabona, J.; Miró Meda, José M. (José María), 1956-; PISCIS study group.; Nomah, D.K.; Reyes-Urueña, J.; Díaz, Y.; Moreno, Silvia; Aceiton, J.; Bruguera, A.; Vivanco-Hidalgo, R.M.; Llibre, J.M.; Domingo, Pere (Domingo Pedrol); Falcó, V.; Imaz, Arkaitz
Background: Factors affecting outcomes of SARS-CoV-2 infection in people living with HIV are unclear. We assessed the factors associated with SARS-CoV-2 diagnosis and severe outcomes among people living with HIV. Methods: We did a retrospective cohort study using data from the PISCIS cohort of people with HIV in Catalonia (Spain) between March 1 and Dec 15, 2020. We linked PISCIS data with integrated health-care, clinical, and surveillance registries through the Public Data Analysis for Health Research and Innovation Program of Catalonia (PADRIS) to obtain data on SARS-CoV-2 diagnosis, chronic comorbidities, as well as clinical and mortality outcomes. Participants were aged at least 16 years in care at 16 hospitals in Catalonia. Factors associated with SARS-CoV-2 diagnoses and severe outcomes were assessed using univariable and multivariable Cox regression models. We estimated the effect of immunosuppression on severe outcomes (hospital admission for >24 h with dyspnoea, tachypnoea, hypoxaemia, asphyxia, or hyperventilation; or death) using Kaplan-Meier survival analysis. Findings: We linked 20 847 (72·8%) of 28 666 participants in the PISCIS cohort with PADRIS data; 13 142 people had HIV. 749 (5·7%) people with HIV were diagnosed with SARS-CoV-2: their median age was 43·5 years (IQR 37·0-52·7), 131 (17·5%) were female, and 618 (82·5%) were male. 103 people with HIV (13·8%) were hospitalised, seven (0·9%) admitted to intensive care, and 13 (1·7%) died. SARS-CoV-2 diagnosis was more common among migrants (adjusted hazard ratio 1·55, 95% CI 1·31-1·83), men who have sex with men (1·42, 1·09-1·86), and those with four or more chronic comorbidities (1·46, 1·09-1·97). Age at least 75 years (5·2, 1·8-15·3), non-Spanish origin (2·1, 1·3-3·4), and neuropsychiatric (1·69, 1·07-2·69), autoimmune disease (1·92, 1·14-3·23), respiratory disease (1·84, 1·09-3·09), and metabolic disease (2·59, 1·59-4·23) chronic comorbidities were associated with increased risk of severe outcomes. A Kaplan-Meier estimator showed differences in the risk of severe outcomes according to CD4 cell count in patients with detectable HIV RNA (p=0·039) but no differences were observed in patients with undetectable HIV RNA (p=0·15). Interpretation: People living with HIV with detectable HIV viraemia, chronic comorbidities, and some subpopulations could be at increased risk of severe outcomes from COVID-19. These groups should be prioritised in clinical management and SARS-CoV-2 vaccination programmes. Funding: Fundació "la Caixa". Translations: For the Catalan, Spanish and Russian translations of the Summary see Supplementary Materials section.
Liposomal sprays for nasal vaccination: a comparative study of cationic and anionic formulations involving stability upon nebulization, sprayability, and in vitro immune activation
(Elsevier, 2025-09-07) Aroffu, Matteo; Fulgheri, Federica; Rached, Rita Abi; Castangia, Ines; Corteggio, Annunziata; Italiani, Paola; D'Apice, Luciana; Sainz-Ramos, Myriam; García-Villén, Fátima; Fernàndez-Busquets, Xavier; Manconi, Maria; Pedraz, José Luis; Manca, Maria Letizia; Fadda, Anna Maria
Nasal immunization is a promising non-invasive route, enabling needle-free self-administration and activating immune cells in the mucosal tissue of the upper airways. This vaccination method is particularly appealing when paired with biocompatible and biodegradable nanocarriers like liposomes, which serve as an effective tool for the nasal delivery of antigenic molecules. In the present study, the model antigen ovalbumin was encapsulated in liposomes using an eco-friendly method. Negative and positive liposomes were formulated with Phospholipon®90 G alone (anionic liposomes) or combined with 1,2-dioleoyl-3-trimethylammonium-propane (cationic DOTAPliposomes). These liposomes were smaller than 130 nm and remained stable for up to 3 months. Their sprayability was assessed based on criteria established by the European Medicines Agency and the Food and Drug Administration for nasal products. Both formulations were easily sprayable, generating droplets larger than 5 μm, which are expected to deposit in the nose while avoiding the lungs. Furthermore, after nebulization, they retained their dimensions, structures, and high encapsulation efficiencies (>70 %). In a co-culture system of dendritic cells and B3Z OT-I hybridoma cells, it was shown that they enhanced antigen elivery and presentation,producing approximately 6–9 times more interleukin-2 compared to the ovalbumin solution. Lastly, when tested on macrophages, they did not induce any proinflammatory effect. However, due to their higher mucoadhesiveness (~88 % vs ~8 %) and better deposition in the posterior nasal cavity (~52 % vs ~43 %) compared to anionic liposomes, cationic DOTAP-liposomes appeared more suitable for nasal administration.
Disclosure of cinnamic acid/4,9-diaminoacridine conjugates as multi-stage antiplasmodial hits
(Elsevier, 2024-04-15) Fonte, Mélanie ; Rôla, Catarina; Santana, Sofia; Avalos Padilla, Yunuen; Fernàndez-Busquets, Xavier; Prudêncio, Miguel ; Gomes, Paula A. C ; Teixeira, Catia Marlene
4,9-diaminoacridines with reported antiplasmodial activity were coupled to different trans-cinnamic acids, delivering a new series of conjugates inspired by the covalent bitherapy concept. The new compounds were more potent than primaquine against hepatic stages of Plasmodium berghei, although this was accompanied by cytotoxic effects on Huh-7 hepatocytes. Relevantly, the conjugates displayed nanomolar activities against blood stage P. falciparum parasites, with no evidence of hemolytic effects below 100 mu M. Moreover, the new compounds were at least 25-fold more potent than primaquine against P. falciparum gametocytes. Thus, the new antiplasmodial hits disclosed herein emerge as valuable templates for the development of multi-stage antiplasmodial drug candidates.
Multicomponent nasal spray delivered via penetration-enhancer containing vesicles (PEVs) for antioxidant and antibacterial protection
(Elsevier, 2025-11-01) Rached, Rita Abi; Shakya, Ashok K.; Manca, Maria Letizia; Aroffu, Matteo; García-Villén, Fátima; Touma, Joe A.; Fernàndez-Busquets, Xavier; Ivanov, Marija; Pedraz, José Luis; Louka, Nicolas; Maroun, Richard G.; Manconi, Maria
In this study, a nasal spray was formulated and tested co-loading grape seed extract, thymol, and camphor in penetration enhancer containing vesicles (PEVs) tailored to synergistically protect the nasal mucosa against oxidative stress and bacterial colonization. Based on their previously demonstrated effects, PEVs were prepared with propylene glycol (PG) and further enriched with carrageenan to promote muco-adhesion. The mean diameter of PG-PEVs was similar to 177 nm, and that of carrageenan PG-PEVs was similar to 194 nm. The polydispersity index ranged from 0.25 to 0.27, confirming the homogeneity of the dispersions. The zeta potential was significantly negative (similar to- 63 mV) and the entrapment efficiency was similar to 88 %, irrespective of vesicle composition. Sprayability studies disclosed that both PG-PEVs and carrageenan-PG-PEVs generated droplets larger than 10 mu m, thus appropriate for the deposition in the nasal cavity. Regional nasal deposition studies, carried out with a realistic nasal replica, highlighted that formulation droplets were deposited in the vestibule and turbinate areas of the nose. The ability of formulations to inhibit protein denaturation confirmed their anti-inflammatory effects. In vitro study with A549 and CuFi-1 cells, underlined that PG-PEVs and especially carrageenan PG-PEVs were nontoxic (viability similar to 140 %) and effectively counteracted cell apoptosis caused by hydrogen peroxide, restoring healthy conditions. The in vivo study in mice demonstrated that grape seed extract, thymol, and camphor-loaded carrageenan PG-PEVs were highly effective in counteracting the proliferation of Staphylococcus aureus.
Preliminary evaluation of the in vitro and in vivo efficacy of a novel nanovesicle-doped nanoemulsion co-loading artemisinin and quercetin as a promising strategy to improve the oral malaria therapy
(Elsevier, 2025-05-01) Fulgheri, Federica; Ramírez Moreno, Miriam; Román Álamo, Lucía ; Gasco, Paolo; Manconi, Maria; Aroffu, Matteo; Rached, Rita Abi; Baroli, Biancamaria; Fernàndez-Busquets, Xavier; Manca, Maria Letizia
Pegylated-liposomes increase the efficacy of Idelalisib in lymphoma B-cells
(Elsevier, 2024-05-25) Maroni, Giorgia; Tomassi, Elena; Valenti, Donatella; Fernàndez-Busquets, Xavier; Pucci, Laura; Levantini, Elena; Caddeo, Carla
New drugs and technologies are continuously developed to improve the efficacy and minimize the critical side effects of cancer treatments. The present investigation focuses on the development of a liposomal formulation for Idelalisib, a small-molecule kinase inhibitor approved for the treatment of lymphoid malignancies. Idelalisib is a potent and selective antitumor agent, but it is not indicated nor recommended for first-line treatment due to fatal and serious toxicities. Herein, liposomes are proposed as a delivery tool to improve the therapeutic profile of Idelalisib. Specifically, PEGylated liposomes were prepared, and their physicochemical and technological features were investigated. Light-scattering spectroscopy and cryo-transmission electron microscopy revealed nanosized unilamellar vesicles, which were proved to be stable in storage and in simulated biological fluids. The cytotoxicity of the liposome formulation was investigated in a human non-Hodgkin's lymphoma B cell line. Idelalisib was able to induce death of tumor cells if delivered by the nanocarrier system at increased efficacy. These findings suggest that combining Idelalisib and nanotechnologies may be a powerful strategy to increase the antitumor efficacy of the drug.
Potentially causal associations between placental DNA methylation and schizophrenia and other neuropsychiatric disorders
(Nature Publishing Group, 2025-03-14) Cilleros-Portet, Ariadna; Lesseur, Corina; Marí, Sergi; Cosín Tomàs, Marta; Lozano Relaño, Manuel; Irizar, Amaia; Burt, Amber; García-Santisteban, Iraia; Garrido Martín, Diego, 1992-; Escaramís Babiano, Geòrgia; Hernangomez-Laderas, Alba; Soler-Blasco, Raquel; Breeze, Charles E.; Gonzalez-Garcia, Bárbara P.; Santa Marina, Loreto; Chen, Jia; Llop, Sabrina; Fernández, Mariana F.; Vrijheid, Martine; Ibarluzea, Jesús; Guxens, Mònica; Marsit, Carmen; Bustamante Pineda, Mariona; Bilbao, Jose Ramon; Fernandez-Jimenez, Nora
Increasing evidence supports the role of the placenta in neurodevelopment and in the onset of neuropsychiatric disorders. Recently, mQTL and iQTL maps have proven useful in understanding relationships between SNPs and GWAS that are not captured by eQTL. In this context, we propose that part of the genetic predisposition to complex neuropsychiatric disorders acts through placental DNA methylation. We construct a public placental cis-mQTL database including 214,830 CpG sites calculated in 368 fetal placenta DNA samples from the INMA project, and run cell type-, gestational age- and sex-imQTL models. We combine these data with summary statistics of GWAS on ten neuropsychiatric disorders using summary-based Mendelian randomization and colocalization. We also evaluate the influence of identified DNA methylation sites on placental gene expression in the RICHS cohort. We find that placental cis-mQTLs are enriched in placenta-specific active chromatin regions, and establish that part of the genetic burden for schizophrenia, bipolar disorder, and major depressive disorder confers risk through placental DNA methylation. The potential causality of several of the observed associations is reinforced by secondary association signals identified in conditional analyses, the involvement of cell type-imQTLs, and the correlation of identified DNA methylation sites with the expression levels of relevant genes in the placenta.
Determinants of early antibody responses to COVID-19 mRNA vaccines in a cohort of exposed and naïve healthcare workers
(Elsevier, 2022-01-11) Moncunill, Gemma; Aguilar, Ruth; Ribes, Marta; Ortega, Natalia; Rubio, Rocío; Salmerón, Gemma; Molina, María José; Vidal, Marta; Barrios, Diana; Mitchell, Robert A.; Jiménez, Alfons; Castellana, Cristina; Hernández-Luis, Pablo; Rodó, Pau; Méndez, Susana; Llupià García, Anna; Puyol, Laura; Rodrigo Melero, Natalia; Carolis, Carlo; Mayor Aparicio, Alfredo Gabriel; Izquierdo, Luis; Varela, Pilar; Trilla Garcia, Antonio De Padua; Vilella, Anna; Barroso, Sonia; Angulo Aguado, Ana; Engel Rocamora, Pablo; Tortajada, Marta; Garcia-Basteiro, Alberto L.; Dobaño, Carlota, 1969-
Background: Two doses of mRNA vaccination have shown >94% efficacy at preventing COVID-19 mostly in naïve adults, but it is not clear if the second dose is needed to maximize effectiveness in those previously exposed to SARS-CoV-2 and what other factors affect responsiveness. Methods: We measured IgA, IgG and IgM levels against SARS-CoV-2 spike (S) and nucleocapsid (N) antigens from the wild-type and S from the Alpha, Beta and Gamma variants of concern, after BNT162b2 (Pfizer/BioNTech) or mRNA-1273 (Moderna) vaccination in a cohort of health care workers (N=578). Neutralizing capacity and antibody avidity were evaluated. Data were analyzed in relation to COVID-19 history, comorbidities, vaccine doses, brand and adverse events. Findings: Vaccination induced robust IgA and IgG levels against all S antigens. Neutralization capacity and S IgA and IgG levels were higher in mRNA-1273 vaccinees, previously SARS-CoV-2 exposed, particularly if symptomatic, and in those experiencing systemic adverse effects (p<0·05). A second dose in pre-exposed did not increase antibody levels. Smoking and comorbidities were associated with 43% (95% CI, 19-59) and 45% (95% CI, 63-18) lower neutralization, respectively, and 35% (95% CI, 3-57%) and 55% (95% CI, 33-70%) lower antibody levels, respectively. Among fully vaccinated, 6·3% breakthroughs were detected up to 189 days post-vaccination. Among pre-exposed non-vaccinated, 90% were IgG seropositive more than 300 days post-infection. Interpretation: Our data support administering a single-dose in pre-exposed healthy individuals as primary vaccination. However, heterogeneity of responses suggests that personalized recommendations may be necessary depending on COVID-19 history and life-style. Higher mRNA-1273 immunogenicity would be beneficial for those expected to respond worse to vaccination and in face of variants that escape immunity such as Omicron. Persistence of antibody levels in pre-exposed unvaccinated indicates maintenance of immunity up to one year. Funding: This work was supported by Institut de Salut Global de Barcelona (ISGlobal) internal funds, in-kind contributions from Hospital Clínic de Barcelona, the Fundació Privada Daniel Bravo Andreu, and European Institute of Innovation and Technology (EIT) Health (grant number 20877), supported by the European Institute of Innovation and Technology, a body of the European Union receiving support from the H2020 Research and Innovation Programme. We acknowledge support from the Spanish Ministry of Science and Innovation and State Research Agency through the "Centro de Excelencia Severo Ochoa 2019-2023" Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. L. I. work was supported by PID2019-110810RB-I00 grant from the Spanish Ministry of Science & Innovation. Development of SARS-CoV-2 reagents was partially supported by the National Institute of Allergy and Infectious Diseases Centers of Excellence for Influenza Research and Surveillance (contract number HHSN272201400008C). The funders had no role in study design, data collection and analysis, the decision to publish, or the preparation of the manuscript.
RBD-Based ELISA and Luminex Predict Anti-SARS-CoV-2 Surrogate-Neutralizing Activity in Two Longitudinal Cohorts of German and Spanish Health Care Workers
(American Society for Microbiology, 2023-02-14) Aguilar, Ruth; Li, Xue; Crowell, Claudia S.; Burrell, Teresa; Vidal, Marta; Rubio, Rocío; Jiménez, Alfons; Hernández-Luis, Pablo; Hofmann, Dieter; Mijočević, Hrvoje; Jeske, Samuel; Christa, Catharina; D'Ippolito, Elvira; Lingor, Paul; Knolle, Percy A; Roggendorf, Hedwig; Priller, Alina; Yazici, Sarah; Carolis, Carlo; Mayor Aparicio, Alfredo Gabriel; Schreiner, Patrik; Poppert, Holger; Beyer, Henriette; Schambeck, Sophia E.; Izquierdo Lázaro, Luis; Tortajada, Marta; Angulo Aguado, Ana; Soutschek, Sophia E.; Engel Rocamora, Pablo; Garcia-Basteiro Alberto L.; Busch, Dirk H; Moncunill Piñas, Gemma; Protzer, Ulrike; Dobaño, Carlota, 1969- ; Gerhard, Markus
The ability of antibodies to neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important correlate of protection. For routine evaluation of protection, however, a simple and cost-efficient anti-SARS-CoV-2 serological assay predictive of serum neutralizing activity is needed. We analyzed clinical epidemiological data and blood samples from two cohorts of health care workers in Barcelona and Munich to compare several immunological readouts for evaluating antibody levels that could be surrogates of neutralizing activity. We measured IgG levels against SARS-CoV-2 spike protein (S), its S2 subunit, the S1 receptor binding domain (RBD), and the full length and C terminus of nucleocapsid (N) protein by Luminex, and against RBD by enzyme-linked immunosorbent assay (ELISA), and assessed those as predictors of plasma surrogate-neutralizing activity measured by a flow cytometry assay. In addition, we determined the clinical and demographic factors affecting plasma surrogate-neutralizing capacity. Both cohorts showed a high positive correlation between IgG levels to S antigen, especially to RBD, and the levels of plasma surrogate-neutralizing activity, suggesting RBD IgG as a good correlate of plasma neutralizing activity. Symptomatic infection, with symptoms such as loss of taste, dyspnea, rigors, fever and fatigue, was positively associated with anti-RBD IgG positivity by ELISA and Luminex, and with plasma surrogate-neutralizing activity. Our serological assays allow for the prediction of serum neutralization activity without the cost, hazards, time, and expertise needed for surrogate or conventional neutralization assays. Once a cutoff is established, these relatively simple high-throughput antibody assays will provide a fast and cost-effective method of assessing levels of protection from SARS-CoV-2 infection. IMPORTANCE Neutralizing antibody titers are the best correlate of protection against SARS-CoV-2. However, current tests to measure plasma or serum neutralizing activity do not allow high-throughput screening at the population level. Serological tests could be an alternative if they are proved to be good predictors of plasma neutralizing activity. In this study, we analyzed the SARS-CoV-2 serological profiles of two cohorts of health care workers by applying Luminex and ELISA in-house serological assays. Correlations of both serological tests were assessed between them and with a flow cytometry assay to determine plasma surrogate-neutralizing activity. Both assays showed a high positive correlation between IgG levels to S antigens, especially RBD, and the levels of plasma surrogate-neutralizing activity. This result suggests IgG to RBD as a good correlate of plasma surrogate-neutralizing activity and indicates that serology of IgG to RBD could be used to assess levels of protection from SARS-CoV-2 infection.
Normalization of short-chain fatty acid concentration by bacterial count of stool samples improves discrimination between eubiotic and dysbiotic gut microbiota caused by Clostridioides difficile infection-
(Taylor & Francis, 2024-10-12) Sayol Altarriba, Anna; Aira Gómez, Andrea; Villasante, Anna; Albarracín, Rosa; Faneca, Joana; Casals Mercadal, Gregori; Villanueva Cañas, José Luis; Casals Pascual, Climent
Short-chain fatty acids (SCFAs) represent a cornerstone of gut health, serving as critical mediators of immune modulation and overall host homeostasis. Patients with dysbiosis caused by Clostridioides difficile infection (CDI) typically exhibit lower SCFAs levels compared to healthy stool donors and, thus, the concentration of SCFAs has been proposed as a proxy marker of a healthy microbiota. However, there is no consistency in the methods used to quantify SCFAs in stool samples and usually, the results are normalized by the weight of the stool samples, which does not address differences in water and fiber content and ignores bacterial counts in the sample (the main component of stool that contributes to the composition of these metabolites in the sample). Here, we show that normalized SCFAs concentrations by the bacterial count improve discrimination between healthy and dysbiotic samples (patients with CDI), particularly when using acetate and propionate levels. After normalization, butyrate is the metabolite that best discriminates eubiotic and dysbiotic samples according to the area under the receiver operating characteristic (ROC) curve (AUC-ROC = 0.860, [95% CI: 0.786–0.934], p < .0001).
Seven-month kinetics of SARS-CoV-2 antibodies and protective role of pre-existing antibodies to seasonal human coronaviruses on COVID-19
(Nature Publishing Group, 2021-08-06) Ortega, Natalia; Ribes, Marta; Vidal, Marta; Rubio, Rocío; Aguilar, Ruth; Williams, Sarah; Barrios, Diana; Alonso, Selena; Hernández-Luis, Pablo; Mitchell, Robert A.; Jairoce, Chenjerai; Cruz, Angeline; Jiménez, Alfons; Santano, Rebeca; Méndez, Susana; Lamoglia Puig, Montserrat; Rosell, Neus; Llupià García, Anna; Puyol, Laura; Chi, Jordi; Rodrigo-Melero, Natalia; Parras, Daniel; Serra, Pau; Pradenas Saavedra, Edwards; Trinité, Benjamin; Blanco, Julià; Mayor Aparicio, Alfredo Gabriel; Barroso, Sonia; Varela, Pilar; Vilella, Anna; Trilla Garcia, Antonio De Padua; Santamaria, Pere; Carolis, Carlo; Tortajada, Marta; Izquierdo Lázaro, Luis; Angulo Aguado, Ana; Engel Rocamora, Pablo ; Garcia-Basteiro, Alberto L; Moncunill Piñas, Gemma; Dobaño, Carlota, 1969-
Unraveling the long-term kinetics of antibodies to SARS-CoV-2 and the individual characteristics influencing it, including the impact of pre-existing antibodies to human coronaviruses causing common cold (HCoVs), is essential to understand protective immunity to COVID-19 and devise effective surveillance strategies. IgM, IgA and IgG levels against six SARS-CoV-2 antigens and the nucleocapsid antigen of the four HCoV (229E, NL63, OC43 and HKU1) were quantified by Luminex, and antibody neutralization capacity was assessed by flow cytometry, in a cohort of health care workers followed up to 7 months (N = 578). Seroprevalence increases over time from 13.5% (month 0) and 15.6% (month 1) to 16.4% (month 6). Levels of antibodies, including those with neutralizing capacity, are stable over time, except IgG to nucleocapsid antigen and IgM levels that wane. After the peak response, anti-spike antibody levels increase from ~150 days post-symptom onset in all individuals (73% for IgG), in the absence of any evidence of re-exposure. IgG and IgA to HCoV are significantly higher in asymptomatic than symptomatic seropositive individuals. Thus, pre-existing cross-reactive HCoVs antibodies could have a protective effect against SARS-CoV-2 infection and COVID-19 disease.
Clinical Variables Related to Functional Capacity and Exertional Desaturation in Patients with COVID-19
(MDPI, 2023-07-20) Larrateguy, Santiago; Vinagre, Julian; Londero, Federico; Dabin, Johana; Ricciardi, Evangelina; Jeanpaul, Santiago; Torres Castro, Rodrigo; Núñez Cortés, Rodrigo; Sánchez Ramírez, Diana; Gimeno Santos, Elena, 1980-; Blanco Vich, Isabel
Impaired functional capacity is one of the most commonly reported consequences among post-COVID-19 patients. This study aimed to analyse the clinical variables related to functional capacity and exertional desaturation in post-COVID-19 patients at the time of hospital discharge. A cross-sectional study was conducted on patients recovering from COVID-19 pneumonia. The main outcomes measures were functional capacity, assessed using the 1 min sit-to-stand test (1 min STST), and exertional desaturation, defined as a drop of ≥4% in the arterial oxygen saturation. Factors used to characterise the participant outcomes included the use of a high-flow nasal cannula (HFNC), prolonged hospitalisation, occurrence of pulmonary embolism during hospitalisation, and underlying comorbidities. A total of 381 participants (mean age = 53.7 ± 13.2 years, 65.6% men) were included. Participants completed a mean of 16.9 ± 6.2 repetitions in the 1 min STST. Exertional desaturation was observed in 51% of the patients. Higher odds of exertional desaturation were found in the participants who used a HFNC (OR = 3.6; 95%CI: 1.6 to 7.8), were admitted in the hospital >10 days (OR = 4.2; 95%CI: 2.6 to 6.8), and had a pulmonary embolism (OR = 3.5; 95%CI: 2.2. to 5.3). Use of a HFNC (β = -3.4; 95%CI: -5.3 to -1.44), a hospital stay >10 days (β = -2.2; 95%CI: -3.4 to -0.9), and a history of pulmonary embolism (β = -1.4; 95%CI: -2.6 to -0.2) were also negatively associated with the 1 min STST. Most post-COVID-19 patients exhibited reduced functional capacity at the time of hospital discharge, and approximately half had exertional desaturation after the 1 min STST. The use of a HFNC, prolonged hospitalisation and pulmonary embolism were the main clinical variables associated with worse a 1 min STST performance and a higher likelihood of exertional desaturation.
Holistic evaluation of the impact of pregnancy urban exposome on infant wheezing and chest infections: an outcome-wide approach
(Elsevier Ltd., 2025-11-08) Gómez Roig, Ma. Dolores; Sunyer, Jordi; Marcon, Alessandro; Johannessen, Ane; Dadvand, Payam; Sinsamala, Robin M.; Anguita-Ruiz, Augusto; Basagaña, Xavier; Foraster, Maria; Gascón, Mireia; Llurba Olivé, Elisa; Luo, Chongliang; Nieuwenhuijsen, Mark J.; Persavento, Cecilia; Rivas, Ioar; Zhao, Yu
Background: Few studies have considered the complex interplay of the urban exposome in association with multiple respiratory outcomes during infancy. Aim: Utilizing an outcome-wide exposome approach, we aimed to assess associations of pregnancy urban exposome with offspring wheezing and chest infections at different time points within the first 18 months of life. Methods: The analysis included data from 1032 mother-child pairs from the Barcelona Life Study Cohort (BiSC) (2018-2021). In total, 44 urban exposome factors were assessed during pregnancy, including air pollution, noise, temperature, humidity, green and blue spaces, and socioeconomic and lifestyle factors. Wheezing and chest infection were evaluated simultaneously at 2, 6, 12, and 18 months. We applied mixed-response sparse reduced-rank regression (MsRRR), with resampling procedures, adjusting for potential confounders. This many-to-many modelling approach identifies exposures concurrently associated with multiple interrelated outcomes. Results: We found 13 exposures consistently associated with wheezing and chest infection across four time-points. Maternal education was the most consistent protective factor with odds ratios (OR) ranging from 0.65 to 0.81 for university and 0.88 to 0.96 for secondary education (vs. primary education) (all p < 0.05). Other important protective factors were size of nearest green space and maternal light-intensity physical activity. NO2 (OR 1.02-1.08), outdoor temperature (OR 1.02-1.04), and noise annoyance (OR 1.01-1.03) were consistently associated with increased risk. Area-level socioeconomic status indicators showed inverse associations. Conclusion: Pregnancy urban exposome may influence both wheezing and chest infections in infancy. Identifying key determinants through an outcome-wide exposome approach can inform targeted public health interventions towards more holistic urban planning strategies.
Agreement and Reliability Between Tele-Assessment and In-Person Assessment of the One-Minute Sit-to-Stand Test in Patients with Chronic Respiratory Diseases
(MDPI, 2025-07-16) Larrateguy, Santiago; Otto Yáñez, Matías; Bogado, Juan; Larrateguy, Luis; Barros Poblete, Marisol; Mazzucco, Guillermo; Blanco Vich, Isabel; Gimeno Santos, Elena, 1980-; Torres Castro, Rodrigo
Background/Objectives: Telemedicine has emerged as a valuable tool for overcoming access barriers in healthcare, particularly in rehabilitation. However, the validity and reliability of remotely conducted physical capacity assessments remain unclear. This study evaluated the agreement and intra-rater reliability between in-person and tele-assessment administration of the one-minute sit-to-stand test (1 min-STST) in individuals with chronic respiratory diseases (CRDs). Methods: In this cross-sectional study, forty adults (55% female; mean age 59.8 ± 15.9 years) diagnosed with CRDs-including chronic obstructive pulmonary disease (52.5%), asthma (20%), and pulmonary fibrosis (20%)-completed the 1 min-STST in two conditions: in person and via tele-assessment. The primary outcome was the number of repetitions completed in each condition. Intra-rater reliability was analyzed using the intraclass correlation coefficient (ICC), and agreement between methods was evaluated with Bland-Altman analysis. Results: The mean number of repetitions was 24.4 ± 8.0 in person and 24.3 ± 8.1 via tele-assessment, with no significant difference (p = 0.78). Excellent reliability was observed (ICC = 0.978, p < 0.001), and Bland-Altman analysis showed good agreement with a mean difference of 0.08 ± 1.7 repetitions and limits of agreement from -3.26 to 3.41. No adverse events were reported. Conclusions: Tele-assessment of the 1 min-STST shows excellent agreement and reliability compared to in-person assessment in individuals with CRDs. These findings support tele-assessment as a valid and practical alternative for evaluating functional capacity remotely. Further research is needed to confirm its implementation in home-based or less-controlled settings.
Effects of pulmonary arterial hypertension therapies on arterial oxygenation in patients with pulmonary hypertension associated with lung disease: a systematic review and meta-analysis
(BMJ Publishing Group, 2025-10-10) Blanco Vich, Isabel; Torres Castro, Rodrigo; Piccari, Lucilla; Roberto Garcia, Agustín; Gimeno Santos, Elena, 1980-; Ramírez, Ana M.; Barberà i Mir, Joan Albert
Background Pulmonary hypertension (PH) associated with lung disease entails a poor prognosis. There is concern about the potential deleterious effect on gas exchange of drugs approved for pulmonary arterial hypertension (PAH) in patients with lung disease. We conducted a systematic review on the effects of drugs approved for PAH on arterial oxygenation in randomised clinical trials (RCTs) conducted in patients with PH associated with lung disease. Methods Five databases were searched until May 2025. We included RCTs with PAH therapies in patients with PH associated with lung disease that reported measurements of arterial oxygenation, either the partial pressure of arterial oxygen (PaO2) or the arterial oxygen saturation (SpO2). For analysis purposes, both measurements were merged into one single variable called ‘overall oxygenation’. As secondary outcomes, we analysed the use of supplemental oxygen and the presence of adverse events related to oxygenation. Results Of the 393 reports returned by the initial search, nine articles, reporting 827 patients (64.6% male), were included. The overall oxygenation at the end of the trial in the intervention group (IG), treated with a PAH therapy, was similar to the control group (standard mean difference (SMD) −0.00; 95% CI −0.17 to 0.18; p=0.98). Similarly, the change in overall oxygenation postintervention in the IG was similar to the control group (SMD 0.01; 95% CI −0.22 to 0.24; p=0.91). Reported adverse events related to oxygenation were similar in the treatment and control arms. Conclusion There is currently no consistent evidence from RCTs to suggest a deleterious effect of PAH therapies on arterial oxygenation in patients with PH associated with lung disease.
Prenatal exposure to synthetic phenols assessed in multiple urine samples and dysregulation of steroid hormone homeostasis in two European cohorts
(National Institute of Environmental Health Science, 2025-05-22) Jedynak, Paulina; Bustamante Pineda, Mariona; Rolland, Matthieu; Mustieles, Vicente; Thomsen, Cathrine; Sakhi, Amrit K.; Sabaredzovic, Azemira; Foraster, Maria; Gascón, Mireia; Gómez Roig, Ma. Dolores; Llurba Olivé, Elisa; Rivas, Ioar; Ouellet-Morin, Isabelle; Bayat, Sam; Lyon-Caen, Sarah; Pozo, Oscar J.; Vrijheid, Martine; Sunyer, Jordi; Slama, Rémy; Dadvand, Payam; Philippat, Claire
Background: Some synthetic phenols alter hormonal pathways involved in successful pregnancy and fetal development. Despite high within-subject temporal variability of phenols, previous studies mostly utilized spot urine samples to assess pregnancy exposure. Herein, we investigated associations between pregnancy exposure to eight phenols assessed in multiple pooled urine samples and steroid hormones assessed in maternal hair reflecting cumulative hormone levels over the previous weeks to months.Methods: We assessed phenol-hormone associations in 928 pregnant women from two pooled cohorts recruited in Spain [Barcelona Life Study Cohort (BiSC), 2018-2021] and France [Assessment of Air Pollution exposure during Pregnancy and Effect on Health (SEPAGES), 2014-2017] using pools of up to 21 samples each, collected in early pregnancy (median gestational age: 18.0 wk), as well as hair collected in late pregnancy (BiSC) or at birth (SEPAGES). We measured two bisphenols, four parabens, benzophenone-3, and triclosan along with metabolites of three adrenal(∑cortisol∑cortisol, ∑cortisone∑cortisone, and 11-dehydrocorticosterone) and two reproductive (progesterone and testosterone) hormones. We ran adjusted linear regressions for each exposure biomarker-outcome pair and Bayesian kernel machine regression for phenols mixture.Results: Bisphenol S was associated with higher cortisol and 11-dehydrocorticosterone concentrations. Propylparaben was associated with lower levels of cortisol, cortisone, and 11-dehydrocorticosterone, while methylparaben was linked to a reduction in cortisol levels. Interestingly, associations identified for parabens were stronger for women carrying female fetuses. No associations for phenol mixture were detected.Conclusions: Our study suggests that pregnancy exposure to bisphenol S and some parabens (propyl- and methylparaben) may affect production of maternal corticosteroid hormones that are important for a successful pregnancy and fetal development.
Functional structure of local connections and differentiation of cerebral cortex areas in the neonate
(Elsevier B.V., 2024-08-08) Falcón Falcón, Carles Maria; Pujol Nuez, Jesús; Blanco Hinojo, Laura; Persavento, Cecilia; Martínez Vilavella, Gerard; Gascón, Mireia; Rivas, Ioar; Vilanova, Marc; Deus Yela, Juan; Gispert, Juan Domingo; Gómez Roig, Ma. Dolores; Llurba Olivé, Elisa; Dadvand, Payam; Sunyer, Jordi
Neuroimaging research on functional connectivity can provide valuable information on the developmental differentiation of the infant cerebral cortex into its functional areas. We examined healthy neonates to comprehensively map brain functional connectivity using a combination of local measures that uniquely capture the rich spatial structure of cerebral cortex functional connections. Optimal functional MRI scans were obtained in 61 neonates. Local functional connectivity maps were based on Iso-Distance Average Correlation (IDAC) measures. Single distance maps and maps combining three distinct IDAC measures were used to assess different levels of cortical area functional differentiation. A set of brain areas showed higher connectivity than the rest of the brain parenchyma in each local distance map. These areas were consistent with those supporting basic aspects of the neonatal repertoire of adaptive behaviors and included the sensorimotor, auditory and visual cortices, the frontal operculum/anterior insula (relevant for sucking, swallowing and the sense of taste), paracentral lobule (processing anal and urethral sphincter activity), default mode network (relevant for self-awareness), and limbicemotional structures such as the anterior cingulate cortex, amygdala and hippocampus. However, the results also indicate that brain areas presumed to be actively developing may not necessarily be mature. In fact, combined distance, second-level maps confirmed that the functional differentiation of the cerebral cortex into functional areas in neonates is far from complete. Our results provide a more comprehensive understanding of the developing brain systems, while also highlighting the substantial developmental journey that the neonatal brain must undergo to reach adulthood.

Examinar

Enviaments recents