52 research outputs found
Broad virus inactivation using inorganic micro/nano-particulate materials
No full textThis publication was also supported by the European
Virus Archive GLOBAL (EVA-GLOBAL) project that has received funding
from the European Union's Horizon 2020 research and innovation program under grant agreement 871029.Rius-Rocabert S, Arranz-Herrero J, Fernández-Valdés A, Marciello M, Moreno S, Llinares-Pinel F, Presa J, Hernandez-Alcoceba R, López-Píriz R, Torrecillas R, García A, Brun A, Filice M, Moya JS, Cabal B, Nistal-Villan
Del acervo comunitario y otras pizzas: contribución de la integración diferenciada a la transformación del acervo
No full textAgua, harina, sal, una pizca de levadura, mozzarella y tomate. Estos
son los ingredientes básicos e imprescindibles de cualquier pizza italiana.
Sin alguno de ellos no existe la vera pizza italiana. Conforman la denominada
pizza margherita. Cualesquiera otros ingredientes que se deseen
suponen un extra que se añade a dicha base. Según los ingredientes que
cada comensal vaya añadiendo en función de su gustó surge una u otra
pizza, con tantas combinaciones como posibilidades ofrezca la riqueza de
las materias primas existentes en la pizzeria elegida para la degustación.
Esta pequeña introducción gastronómica sirve para ilustrar perfectamente
la relación que los terceros Estados que quieren adherirse a la Comunidad
tienen, de una parte, con el acervo comunitario en sentido estricto
y, de otra, con el acervo que surge de la integración diferenciada practicada
en el interior de la Comunidad; igualmente ilustra la relación de los
Estados miembros con el acervo de la integración diferenciada. Como
veremos, desde la introducción de la integración diferenciada en la Comunidad,
el acervo comunitario se ha convertido en el mínimo común
denominador que los terceros Estados deben aceptar para adherirse a la
Comunidad; una especie de pizza margherita. Sobre él, los nuevos Estados
pueden elegir, además, participar o no en ámbitos concretos en los
que se practica una mayor integración por sólo algunos Estados miembros;
nace así un elenco variado de derechos y obligaciones para los nuevos
Estados miembros en función de su elección; una especie de pizza formada
por una base margherita con ingredientes añadidos. Del mismo modo,
los que ya son Estados miembros pueden elegir en un determinado momento
participar o no en una mayor integración en un ámbito concreto en
la Comunidad, componiendo a la carta su particular pizza de derechos y
obligaciones dentro de la Comunidad.____________________________________De l'eau, de la farine, du sel, une pincée de levure, de la mozzarella et de la
tomate. Tels sont les ingrédients de base de n'importe qu'elle pizza italienne. Si quelqu'un
d'eux manque, ce n'est plus une vera pizza italiana. lis conforment la pizza
margherita. Tout un autre ingrédient qu'on veuille y ajouter serait un extra. Selon
les ingrédients que chacun des convives ajoutera á son grée, on obtiendra des différentes
pizzas, resultantes d'autant de combinaisons que des possibilités nous offrent
les matiéres premieres fournies par la pizzeria en question. L'auteur s'est servie de
cette introduction gastronomique pour illustrer le rapport des États tiers candidats á
l'adhésion a l'Union Européenne avec, d'une part l'acquis communautaire stricto
sensu et, d'une autre avec l'acquis résultant de l'intégration différenciée. L'image
montre également la relation des États membres avec l'intégration différenciée actuellement
pratiquée au sein de la Communauté. Depuis 1'introduction de Pintégration
différenciée dans la Communauté, l'acquis communautaire est devenu le plus
petit dénominateur commun que les États tiers candidats devront accepter pour devenir
membres (une pizza margherita). Une fois celui-ci accepté, ils pourront choisir
participer ou pas aux autres circuits oü il existe deja une plus grande integration
entre certains États membres: de cette sorte, il naítra toute une varíete de droits et
d'obligations pour chaqué nouveau État membre, d'aprés son propre choix (une pizza
avec une base de margherita plus les ingrédients extra ajoutés). D'une fafon analogue,
les États membres actuéis peuvent choisir participer ou pas á une plus grande
integration au sein de la Communauté, composant á la carte leur propre pizza de
droits et d'obligations dans la Communauté.
L'auteur revise aussi les différents concepts du terme «acquis communautaire»
et ses rapports avec l'acquis de l'intégration différenciée et celui de l'Union.____________________________________________Water, flour, a pinch of yeast, mozzarella and tomato. These are the basic and
essential ingredients of any Italian pizzza. They compose the so-called pizza margherita.
Any other ingredient that we wish to add would be an extra to that base.
Depending on the ingredients that any of the guests at the table would like to add,
there would result as many pizzas as combinations could be created with the possibilities
offered by that the raw materials available at the pizzería. This short gastronomic
introduction serves us to illustrate the relationship between the Candidate States
to the European Union and, on one side the acquis communautaire stricto sensu and,
on the other side, the acquis resulting from the differentiated integration that have
been practiced within the European Community. It also shows the relationship between
the current Member States and the acquis on differentiated integration. As we
will see, since the introduction of the differentiated integration in the European
Community, the acquis communautaire has become the lowest common denominator
that the Candidate States must accept should they want to enter in the European
Community; it is, then, like the aforementioned pizza margherita. On this basis, the
new Member States would be able to chose whether they wish to take part or not
on specific áreas where a deeper integration is exercised by only certain Member
States. Thus, a wide variety of rights and obligations arises for the new Member
States, according to their own choice: like a pizza made of a margherita basis where
several ingredients had been added on the top. In the same way, the current Member
States are able to chose to particípate or not in a deeper integration within the
Community. In so doing, they créate a la carte their own particular pizza on rights
and obligations within the European Community. The author shows the different concepts of acquis communautaire and their relationship
with the acquis of differentiated integration and the acquis of the Union
as well.Publicad
Rituximab and the risk of transformation of follicular lymphoma: a retrospective pooled analysis
No full textBackground: Histological transformation of follicular lymphoma to aggressive lymphoma is a serious event with a substantial effect on patient outcome. The aim of the Aristotle study was to assess the effect of rituximab on the risk of histological transformation and its outcome. Methods: 11 cooperative groups or institutions across Europe contributed data to this study. Eligible patients (≥18 years) had histologically confirmed follicular lymphoma grade 1, 2, or 3a, diagnosed between Jan 2, 1997, and Dec 20, 2013. Histological transformation was defined as a biopsy-proven aggressive lymphoma that occurred as a first event after first-line therapy. The primary endpoints were the cumulative hazard of histological transformation and survival after transformation. Findings: Information was available for 10 001 patients with follicular lymphoma, 8116 of whom were eligible for analysis. 509 histological transformations were reported. After a median follow-up of 87 months (range 1–221; 2·5–97·5th percentile 5–160), the 10-year cumulative hazard of histological transformation was 7·7% (95% CI 6·9–8·5). The 10-year cumulative hazard of histological transformation was 5·2% (95% CI 4·5–6·2) in patients who received rituximab and 8·7% (7·2–10·6) in those who did not (hazard ratio [HR] 0·73, 95% CI 0·58–0·90; p=0·004). The 10-year cumulative hazard of histological transformation was 5·9% (95% CI 5·0–7·0) for patients who received induction rituximab only and 3·6% (95% CI 2·3–5·5) for those treated with induction and maintenance rituximab (HR 0·55, 95% CI 0·37–0·81; p=0·003). This finding was confirmed in a multivariate analysis (p=0·016). 287 deaths were recorded in 509 patients with histological transformation, resulting in a 10-year survival after transformation of 32% (95% CI 26–38). Survival after transformation did not differ between patients not exposed to rituximab and those who received rituximab in induction only (HR 0·94, 95% CI 0·69–1·28; p=0·70), and those who received rituximab in induction and maintenance (0·96, 0·58–1·61; p=0·88). Interpretation: The risk of histological transformation as a first event can be significantly reduced by the use of rituximab. These findings support the need to inform patients using rituximab nowadays that the risk of transformation is lower than it was before the introduction of rituxumab. Funding: Associazione Angela Serra per la Ricerca sul Cancro, European Lymphoma Institute, European Hematology Association Lymphoma Group, Fondazione Italiana Linfomi, Spanish Group of Lymphoma and Bone Marrow Transplantation
Differential contribution of PBP occupancy and efflux on the effectiveness of β-lactams at their target site in clinical isolates of Neisseria gonorrhoeae.
No full textNeisseria gonorrhoeae exhibits alarming antibiotic resistance trends and poses a significant challenge in therapeutic management. This study aimed to explore the association of penA alleles with penicillin-binding protein (PBP) occupancy patterns and reduced outer membrane permeability, impacting susceptibility to last-line cephalosporins and potential β-lactam candidates. The whole genome sequence, the MICs and PBP IC50s were determined for 12 β-lactams and β-lactamase inhibitors in 8 clinical isolates with varying β-lactam sensitivity, 2 ATCC, and 3 WHO cephalosporin-resistant reference strains. The genetic analysis identified diverse determinants of β-lactam resistance including penA, ponA, porB, and mtrR alterations. Mosaic penA alleles were confirmed to be key determinants of cephalosporin resistance, with notable impacts on PBP2 IC50 affinities (in the presence of all PBPs). Substitutions in positions V316 and A501 exhibited significant effects on β-lactam PBP2 occupancy and MICs. PBP1 inhibition showed marginal effect on β-lactam sensitivity and PBP3 acted as a sink target. Ertapenem and piperacillin emerged as potential therapies against cephalosporin-resistant N. gonorrhoeae strains, along with combination therapies involving tazobactam and/or efflux inhibitors. The study determined the β-lactam PBP-binding affinities of last-line cephalosporins and alternative β-lactam candidates in strains carrying different penA alleles for the first time. These findings provide insights for developing new antimicrobial agents and enhancers against emerging resistant strains. Further research is warranted to optimize therapeutic interventions for cephalosporin-resistant N. gonorrhoeae infections
A Case of Aeromonas trota in an Immunocompromised Patient with Diarrhea
No full textAccording to recent literature, 95.4% of the Aeromonas strains associated with human clinical cases correspond to four species: Aeromonas caviae, Aeromonas dhakensis, Aeromonas veronii and Aeromonas hydrophila. However, other less prevalent species such as Aeromonas trota, are also described from clinical samples. Based on its low incidence, the latter species can be regarded as rare and it is the only Aeromonas species susceptible to ampicillin. From the taxonomic point of view, A. trota is considered a synonym of the species Aeromonas enteropelogenes. The objective of this study is to present a new clinical case associated with A. trota in order to increase the knowledge about this species. The strain was recovered from the feces of a 69-year-old patient with a diarrheal syndrome and peritoneal psammocarcinoma. The preliminary identification as Aeromonas sp. was obtained with the API 20E, but it was characterized as Aeromonas jandei and also as Aeromonas enteropelogenes with different scores with the matrix-assisted laser desorption ionization time of flight (MALDI-TOF). Based on the sequence of the rpoD gene, it was confirmed to be A. trota. The antimicrobial resistance pattern showed that the strain was susceptible to ampicillin, penicillins in combination with beta-lactamase inhibitors, quinolones, carbapenems, aminoglycosides and cephalosporins, except cephalothin. In conclusion, the recognition of an Aeromonas strain susceptible to ampicillin should alert the clinical microbiologist of the possible involvement of this rare species. Furthermore, the MALDI-TOF database should be updated indicating that the species A. enteropelogenes, is a synonym of A. trota
Safety of Adrenaline Use in Anaphylaxis: A Multicentre Register
No full text<b><i>Background:</i></b> The use of intramuscular adrenaline to treat anaphylaxis is suboptimal, despite being the first-line treatment recommended by national and international anaphylaxis guidelines. Fear of potentially severe side effects may be one of the underlying factors. The aim of this study was to assess the incidence and severity of adverse side effects after the use of adrenaline in anaphylaxis, as well as potential risk factors. <b><i>Methods:</i></b> Observational study based on a multicenter online registry of cases of adrenaline administration for suspected anaphylaxis. <b><i>Results:</i></b> 277 registered valid cases were included: 138 (51.49%) female, median age 29 years (12-47), and 6 children under 2 years with a median age of 9 months (1-21). Side effects occurred in 58 cases (21.64%), with tremors, palpitations, and anxiety being the most frequent. There was a significant association of developing side effects with older age, higher dose of adrenaline, or use of the intravenous route. Potentially severe adverse effects (high blood pressure, chest discomfort, or ECG alterations) occurred only in 8 cases (2.99%); in these cases, no differences were found according to age or adrenaline dose, but again, intravenous administration was associated with more severe adverse events. <b><i>Conclusion:</i></b> This study shows that side effects affect less than 1 in 5 patients who receive adrenaline for an anaphylactic reaction, and are usually mild and transient. Therefore, in an emergency situation such as anaphylaxis, restricting adrenaline administration due to potential adverse effects would, in general, not be justified.</jats:p
Fluconazole-resistant Candida parapsilosis clonally related genotypes: first report proving the presence of endemic isolates harbouring the Y132F ERG11 gene substitution in Spain
No full textObjectives: We report here for the first time the presence of Candida parapsilosis isolates harbouring the Y132F ERG11 gene substitution in patients admitted to a Spanish hospital.
Methods: We studied the available (n = 104) C parapsilosis isolates from patients admitted to the Son Espases reference hospital in the Balearic Islands from 1 April 2019 to 30 November 2020. Isolates were sourced from 70 patients: catheter (n = 41), blood cultures (n = 37), lower respiratory tract (n = 15), intra-abdominal (n = 8), and other samples (n = 3). Isolates were genotyped and tested for antifungal susceptibilities to amphotericin B, triazoles, anidulafungin, and micafungin using EUCAST E.Def 7.3.2. The ERG11 gene was sequenced in fluconazole-resistant isolates.
Results: Among the 104 isolates, fluconazole and voriconazole resistance was found in 87 (84%) and 30 (29%) isolates, respectively; all isolates were fully susceptible to echinocandins and amphotericin B. All fluconazole-resistant isolates harboured the Y132F substitution in the ERG11 gene and were grouped into 11 clonally related genotypes. A genotype accounted for 70% (61/87) of fluconazole-resistant isolates. Genotypes involving the fluconazole-resistant isolates were different from those found in the remaining fluconazole-susceptible genotypes. Fifty-six patients harboured fluconazole-resistant genotypes, and 35 of the 56 had candidaemia (48%), abdominal candidiasis (17%), or other forms of candidiasis (35%). Only 20% of the study patients infected by fluconazole-resistant genotypes had a history of azole use.
Discussion: Fluconazole resistance in C parapsilosis isolates from patients admitted to this reference hospital is not attributable to prior azole use, but rather to the presence of a group of fluconazole-resistant C parapsilosis genotypes that have become endemi
Adenovirus-Mediated Inducible Expression of a PD-L1 Blocking Antibody in Combination with Macrophage Depletion Improves Survival in a Mouse Model of Peritoneal Carcinomatosis
No full textImmune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in a growing number of malignancies. However, overcoming primary or secondary resistances is difficult due to pharmacokinetics issues and side effects associated with high systemic exposure. Local or regional expression of monoclonal antibodies (mAbs) using gene therapy vectors can alleviate this problem. In this work, we describe a high-capacity adenoviral vector (HCA-EFZP-aPDL1) equipped with a mifepristone-inducible system for the controlled expression of an anti-programmed death ligand 1 (PD-L1) blocking antibody. The vector was tested in an immune-competent mouse model of colorectal cancer based on implantation of MC38 cells. A single local administration of HCA-EFZP-aPDL1 in subcutaneous lesions led to a significant reduction in tumor growth with minimal release of the antibody in the circulation. When the vector was tested in a more stringent setting (rapidly progressing peritoneal carcinomatosis), the antitumor effect was marginal even in combination with other immune-stimulatory agents such as polyinosinic-polycytidylic acid (pI:C), blocking mAbs for T cell immunoglobulin, mucin-domain containing-3 (TIM-3) or agonistic mAbs for 4-1BB (CD137). In contrast, macrophage depletion by clodronate liposomes enhanced the efficacy of HCA-EFZP-aPDL1. These results highlight the importance of addressing macrophage-associated immunoregulatory mechanisms to overcome resistance to ICIs in the context of colorectal cancer
Broad virus inactivation using inorganic micro/nano-particulate materials
No full textInorganic materials can provide a set of tools to decontaminate solid, liquid or air containing viral particles. The use of disinfectants can be limited or not practical in scenarios where continuous cleaning is not feasible. Physicochemical differences between viruses raise the need for effective formulations for all kind of viruses. In the present work we describe two types of antimicrobial inorganic materials: i) a novel soda-lime glass (G3), and ii) kaolin containing metals nanoparticles (Ag or CuO), as materials to disable virus infectivity. Strong antiviral properties can be observed in G3 glass, and kaolin-containing nanoparticle materials showing a reduction of viral infectivity close to 99%. in the first 10 min of contact of vesicular stomatitis virus (VSV). A potent virucidal activity is also present in G3 and kaolin containing Ag or CuO nanoparticles against all kinds of viruses tested, reducing more than 99% the amount of HSV-1, Adenovirus, VSV, Influenza virus and SARS-CoV-2 exposed to them. Virucidal properties could be explained by a direct interaction of materials with viruses as well as inactivation by the presence of virucidal elements in the material lixiviates. Kaolin-based materials guarantee a controlled release of active nanoparticles with antiviral activity. Current coronavirus crisis highlights the need for new strategies to remove viruses from contaminated areas. We propose these low-cost inorganic materials as useful disinfecting antivirals in the actual or future pandemic threats.This research was performed with support from The Spanish National Research Council (CSIC) (Project No 202060E109). M.F. is grateful to the Comunidad Autonoma de Madrid for research project No. 2017-T1/BIO-4992 (“Atracción de Talento” Action) cofunded by Universidad Complutense de Madrid. This publication was also supported by the European Virus Archive GLOBAL (EVA-GLOBAL) project that has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement 871029. S. R.-R. was supported by the the FPI fellowship funded by Universidad San Pablo CEU. J.A-H. was supported by the PFIS fellowship co-funded by the FEDER/FSE and the ISCIII
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