Silica Particle based nanocomposites for Specific IgE Determination to Betalactams

Current immunoassays for diagnosing betalactam (BL) allergy have limited sensitivity and poor specificity. These include ImmunoCAP, the commercial immunoassay, and the radioallergosorbent test (RAST), a handmade test performed only in specialized laboratories. Both are based on cellulose polymers modified with covalently attachedbetalactam-poly-L-lysine conjugates, which are able to interact with specific IgE (sIgE). In RAST, dendrimers have been used instead of poly-L-lysine in the formation of penicilloyl- conjugates, showing specific recognition by penicillin-sIgE. In this work, we propose the use of nanomaterials consisting on silica particles highly functionalized with drug-dendrimer conjugates (including mono- and bi-epitopic structures), as precise and controlled solid phases able to improve the tests’ reliability. The homogeneous composition of the nano-composites provides high reproducibility and quality, which is critical for hospital applications, while silica particles possess promising properties as biocompatibility, tuneable size, and functionalisation, and their preparation is affordable and reproducible. The use of nano-scaled silica particles improved the results of available immunoassays techniques in terms of sensitivity and specificity, providing the possibility of testing different betalactams, simultaneously.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Ciudad y arquitectura moderna en Colombia: 1950-1970: presencia y vigencia del patrimonio moderno

Postprint (published version

Synthetic antigenic determinants of clavulanic acid induce dendritic cell maturation and specific T cell proliferation in patients with immediate hypersensitivity reactions

Background Immediate drug hypersensitivity reactions (IDHRs) to clavulanic acid (CLV) have increased in the last decades due to a higher consumption alongside amoxicillin (AX). Due to its chemical instability, diagnostic procedures to evaluate IDHRs to CLV are difficult, and current in vitro assays do not have an optimal sensitivity. The inclusion of the specific metabolites after CLV degradation, which are efficiently recognised by the immune system, could help to improve sensitivity of in vitro tests. Methods Recognition by dendritic cells (DCs) of CLV and the synthetic analogues of two of its hypothesised antigenic determinants (ADs) was evaluated by flow cytometry in 27 allergic patients (AP) and healthy controls (HC). Their ability to trigger the proliferation of T cells was also analysed by flow cytometry. Results The inclusion of synthetic analogues of CLV ADs, significantly increased the expression of maturation markers on DCs from AP compared to HC. A different recognition pattern could be observed with each AD, and, therefore, the inclusion of both ADs achieves an improved sensitivity. The addition of synthetic ADs analogues increased the proliferative response of CD4+Th2 compared to the addition of native CLV. The combination of results from both ADs increased the sensitivity of proliferative assays from 19% to 65% with a specificity higher than 90%. Conclusions Synthetic ADs from CLV are efficiently recognised by DCs with ability to activate CD4+Th2 cells from AP. The combination of analogues from both ADs, significantly increased the sensitivity of DC maturation and T-cell proliferation compared to native CLV.This work has been supported by Institute of Health ‘Carlos III’ (ISCIII) of the Ministry of Economy and Competitiveness (MINECO) (grants co-funded by European Regional Development Fund: PI15/01206, PI17/01237, PI18/00095, PI20/01734, RETICS ARADYAL RD16/0006/0001); Andalusian Regional Ministry of Health (grants PI-0241-2016, PE-0172-2018, PI-0127-2020); Spanish Ministerio de Ciencia e Innovación (Proyectos de I+D+I «Programación Conjunta Internacional», EuroNanoMed 2019 (PCI2019-111825-2), Ministerio de Ciencia y Educación (PID2019-104293GB-I00), Instituto de Salud Carlos III (ISCIII) of MINECO (RD16/0006/0012), Junta de Andalucía ( PY20_00384 ). AA and NPS hold Senior Postdoctoral Contracts (RH-0099-2020 and RH-0085-2020) from Andalusian Regional Ministry of Health (cofunded by European Social Fund (ESF): ‘Andalucía se mueve con Europa’). JLP holds a Sara Borrell fellowship (CD19/00250) by ISCIII of MINECO (cofunded by ESF, “El FSE invierte en futuro”). GB holds a ‘Juan Rodes’ contract (JR18/00054) by ISCIII of MINECO (cofunded by ESF). MIM holds a ‘Miguel Servet II’ grant (CPII20/00028) by ISCIII of MINECO (cofunded by ESF). ML holds a ‘Rio Hortega’ contract (CM20/00210) by ISCIII of MINECO (cofunded by ESF). CM holds a ‘Nicolas Monardes’ research contract by Andalusian Regional Ministry Health (RC-0004-2021). NMR experiments for characterizing molecule structures have been performed in the ICTS ‘NANBIOSIS’, by the U28 Unit at the Andalusian Centre for Nanomedicine and Biotechnology (BIONAND). Funding for open access charge: Universidad de Málag

Dendrímeros antigénicos sobre partículas de sílica para determinar IgE específicas de antibióticos betalactámicos

Los inmunoensayos empleados para el diagnóstico in vitro de alergias a antibióticos betalactámicos actualmente presentan una limitada sensibilidad y pobre especificidad, además de no estar disponibles de forma comercial para todos los antibióticos implicados en procesos alérgicos. En este trabajo, se han diseñado nanopartículas de sílica altamente funcionalizadas con dendrímeros y conjugadas con amoxicilina y bencilpenicilina con objeto de mejorar el diagnóstico clínico in vitro de alergia a estos antibióticos.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Evolution of Quality of Life and Treatment Adherence after One Year of Intermittent Bladder Catheterisation in Functional Urology Unit Patients

Objective: To determine patient difficulties and concerns when performing IBC (Intermittent Bladder Catheterisation), as well as the evolution of adherence, quality of life, and emotional state of patients one year after starting IBC. Method: A prospective, observational, multicentre study conducted in 20 Spanish hospitals with a one-year follow-up. Data sources were patient records and the King's Health Questionnaire on quality of life, the Mini-Mental State Examination (MMSE), and the Hospital Anxiety and Depression Scale (HADS). Perceived adherence was measured using the ICAS (Intermittent Catheterization Adherence Scale) and perceived difficulties with IBC were assessed using the ICDQ (Intermittent Catheterization Difficulty Questionnaire). For data analysis, descriptive and bivariate statistics were performed for paired data at three points in time (T1: one month, T2: three months, T3: one year). Results: A total of 134 subjects initially participated in the study (T0), becoming 104 subjects at T1, 91 at T2, and 88 at T3, with a mean age of 39 years (standard deviation = 22.16 years). Actual IBC adherence ranged from 84.8% at T1 to 84.1% at T3. After one year of follow-up, a statistically significant improvement in quality of life (p <= 0.05) was observed in all dimensions with the exception of personal relationships. However, there were no changes in the levels of anxiety (p = 0.190) or depression (p = 0.682) at T3 compared to T0. Conclusions: Patients requiring IBC exhibit good treatment adherence, with a significant proportion of them performing self-catheterisation. After one year of IBC, a significant improvement in quality of life was noted, albeit with a significant impact on their daily lives and their personal and social relationships. Patient support programmes could be implemented to improve their ability to cope with difficulties and thus enhance both their quality of life and the maintenance of their adherence

Hyperspectral image processing for the identification and quantification of lentiviral particles in fluid samples

Optical spectroscopic techniques have been commonly used to detect the presence of biofilm-forming pathogens (bacteria and fungi) in the agro-food industry. Recently, near-infrared (NIR) spectroscopy revealed that it is also possible to detect the presence of viruses in animal and vegetal tissues. Here we report a platform based on visible and NIR (VNIR) hyperspectral imaging for non-contact, reagent free detection and quantification of laboratory-engineered viral particles in fluid samples (liquid droplets and dry residue) using both partial least square-discriminant analysis and artificial feed-forward neural networks. The detection was successfully achieved in preparations of phosphate buffered solution and artificial saliva, with an equivalent pixel volume of 4 nL and lowest concentration of 800 TU.mu L-1. This method constitutes an innovative approach that could be potentially used at point of care for rapid mass screening of viral infectious diseases and monitoring of the SARS-CoV- 2 pandemic.This research was funded by grants number COV20-00080 and COV20-00173 of the 2020 Emergency Call for Research Projects about the SARS-CoV-2 virus and the COVID-19 disease of the Institute of Health 'Carlos III', Spanish Ministry of Science and Innovation, and by grant number EQC2019-006240-P of the 2019 Call for Acquisition of Scientific Equipment, FEDER Program, Spanish Ministry of Science and Innovation. This work has been supported by the European Commission through the JRC HUMAINT project. ABR was supported by grant number RTI2018-094465-J funded by the Spanish National Agency of Research. The authors would like to gratefully acknowledge the assistance of the members of the EOD-CBRN Group of the Spanish National Police, whose identities cannot be disclosed, and who are represented here by JMNG. Authors thank continuous support from their institutions

Risk factors for developing ventilator-associated lower respiratory tract infection in patients with severe COVID-19:a multinational, multicentre study, prospective, observational study

Around one-third of patients diagnosed with COVID-19 develop a severe illness that requires admission to the Intensive Care Unit (ICU). In clinical practice, clinicians have learned that patients admitted to the ICU due to severe COVID-19 frequently develop ventilator-associated lower respiratory tract infections (VA-LRTI). This study aims to describe the clinical characteristics, the factors associated with VA-LRTI, and its impact on clinical outcomes in patients with severe COVID-19. This was a multicentre, observational cohort study conducted in ten countries in Latin America and Europe. We included patients with confirmed rtPCR for SARS-CoV-2 requiring ICU admission and endotracheal intubation. Only patients with a microbiological and clinical diagnosis of VA-LRTI were included. Multivariate Logistic regression analyses and Random Forest were conducted to determine the risk factors for VA-LRTI and its clinical impact in patients with severe COVID-19. In our study cohort of 3287 patients, VA-LRTI was diagnosed in 28.8% [948/3287]. The cumulative incidence of ventilator-associated pneumonia (VAP) was 18.6% [610/3287], followed by ventilator-associated tracheobronchitis (VAT) 10.3% [338/3287]. A total of 1252 bacteria species were isolated. The most frequently isolated pathogens were Pseudomonas aeruginosa (21.2% [266/1252]), followed by Klebsiella pneumoniae (19.1% [239/1252]) and Staphylococcus aureus (15.5% [194/1,252]). The factors independently associated with the development of VA-LRTI were prolonged stay under invasive mechanical ventilation, AKI during ICU stay, and the number of comorbidities. Regarding the clinical impact of VA-LRTI, patients with VAP had an increased risk of hospital mortality (OR [95% CI] of 1.81 [1.40-2.34]), while VAT was not associated with increased hospital mortality (OR [95% CI] of 1.34 [0.98-1.83]). VA-LRTI, often with difficult-to-treat bacteria, is frequent in patients admitted to the ICU due to severe COVID-19 and is associated with worse clinical outcomes, including higher mortality. Identifying risk factors for VA-LRTI might allow the early patient diagnosis to improve clinical outcomes. Trial registration: This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable

The Helicobacter pylori Genome Project : insights into H. pylori population structure from analysis of a worldwide collection of complete genomes

Helicobacter pylori, a dominant member of the gastric microbiota, shares co-evolutionary history with humans. This has led to the development of genetically distinct H. pylori subpopulations associated with the geographic origin of the host and with differential gastric disease risk. Here, we provide insights into H. pylori population structure as a part of the Helicobacter pylori Genome Project (HpGP), a multi-disciplinary initiative aimed at elucidating H. pylori pathogenesis and identifying new therapeutic targets. We collected 1011 well-characterized clinical strains from 50 countries and generated high-quality genome sequences. We analysed core genome diversity and population structure of the HpGP dataset and 255 worldwide reference genomes to outline the ancestral contribution to Eurasian, African, and American populations. We found evidence of substantial contribution of population hpNorthAsia and subpopulation hspUral in Northern European H. pylori. The genomes of H. pylori isolated from northern and southern Indigenous Americans differed in that bacteria isolated in northern Indigenous communities were more similar to North Asian H. pylori while the southern had higher relatedness to hpEastAsia. Notably, we also found a highly clonal yet geographically dispersed North American subpopulation, which is negative for the cag pathogenicity island, and present in 7% of sequenced US genomes. We expect the HpGP dataset and the corresponding strains to become a major asset for H. pylori genomics