Non-perturbative renormalization of lattice four-fermion operators without power subtractions

A general nonperturbative analysis of the renormalization properties of Delta I = 3/2 four-fermion operators in the framework of lattice regularization with Wilson fermions is presented. We discuss the nonperturbative determination of the operator renormalization constants in the lattice regularization independent (RI or MOM) scheme. We also discuss the determination of the finite lattice subtraction coefficients from Ward identities. We prove that, at large external virtualities, the determination of the lattice mixing coefficients, obtained using the RI renormalization scheme, is equivalent to that based on Ward identities, in the continuum and chiral limits. As a feasibility study of our method, we compute the mixing matrix at several renormalization scales, for three Values of the lattice coupling beta, using the Wilson and tree-level improved SW-Clover actions

Molecular signatures of silencing suppression degeneracy from a complex RNA virus

[EN] As genomic architectures become more complex, they begin to accumulate degenerate and redundant elements. However, analyses of the molecular mechanisms underlying these genetic architecture features remain scarce, especially in compact but sufficiently complex genomes. In the present study, we followed a proteomic approach together with a computational network analysis to reveal molecular signatures of protein function degeneracy from a plant virus (as virus-host protein-protein interactions). We employed affinity purification coupled to mass spectrometry to detect several host factors interacting with two proteins of Citrus tristeza virus (p20 and p25) that are known to function as RNA silencing suppressors, using an experimental system of transient expression in a model plant. The study was expanded by considering two different isolates of the virus, and some key interactions were confirmed by bimolecular fluorescence complementation assays. We found that p20 and p25 target a common set of plant proteins including chloroplastic proteins and translation factors. Moreover, we noted that even specific targets of each viral protein overlap in function. Notably, we identified argonaute proteins (key players in RNA silencing) as reliable targets of p20. Furthermore, we found that these viral proteins preferentially do not target hubs in the host protein interactome, but elements that can transfer information by bridging different parts of the interactome. Overall, our results demonstrate that two distinct proteins encoded in the same viral genome that overlap in function also overlap in their interactions with the cell proteome, thereby highlighting an overlooked connection from a degenerate viral system.This work was supported by the grants PROMETEO/2019/012 from the Valencian Regional Government (to SA), as well as grants AGL2010-20221/AGR, BIO2017-83184-R, and PGC2018-101410-B-I00 from the Spanish Ministry of Science, Innovation, and Universities (to SA, JAD, and GR, respectively). The two latter grants were co-financed by the European Regional Development Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ambrós, S.; Gómez-Muñoz, N.; Giménez-Santamarina, S.; Sánchez-Vicente, J.; Navarro-López, J.; Martínez, F.; Daròs, J.... (2021). Molecular signatures of silencing suppression degeneracy from a complex RNA virus. PLoS Computational Biology. 17(6):1-21. https://doi.org/10.1371/journal.pcbi.1009166S12117

Comparison of visual and optical quality of monofocal versus multifocal intraocular lenses

Postprint (author's final draft

Bicuculline Reduces Neuroinflammation in Hippocampus and Improves Spatial Learning and Anxiety in Hyperammonemic Rats. Role of Glutamate Receptors

Patients with liver cirrhosis may develop minimal hepatic encephalopathy (MHE) with mild cognitive impairment. Hyperammonemia is a main contributor to cognitive impairment in MHE, which is mediated by neuroinflammation. GABAergic neurotransmission is altered in hyperammonemic rats. We hypothesized that, in hyperammonemic rats, (a) enhanced GABAergic tone would contribute to induce neuroinflammation, which would be improved by reducing GABAergic tone by chronic bicuculline treatment; (b) this would improve spatial learning and memory impairment; and (c) modulation of glutamatergic neurotransmission would mediate this cognitive improvement. The aim of this work was to assess the above hypotheses. Bicuculline was administrated intraperitoneally once a day for 4 weeks to control and hyperammonemic rats. The effects of bicuculline on microglia and astrocyte activation, IL-1β content, on membrane expression of AMPA and NMDA glutamate receptors subunits in the hippocampus and on spatial learning and memory as well as anxiety were assessed. Treatment with bicuculline reduces astrocyte activation and IL-1β but not microglia activation in the hippocampus of hyperammonemic rats. Bicuculline reverses the changes in membrane expression of AMPA receptor subunits GluA1 and GluA2 and of the NR2B (but not NR1 and NR2A) subunit of NMDA receptors. Bicuculline improves spatial learning and working memory and decreases anxiety in hyperammonemic rats. In hyperammonemia, enhanced activation of GABAA receptors in the hippocampus contributes to some but not all aspects of neuroinflammation, to altered glutamatergic neurotransmission and to impairment of spatial learning and memory as well as anxiety, all of which are reversed by reducing activation of GABAA receptors with bicuculline

Autoimmune Diseases and COVID-19 as Risk Factors for Poor Outcomes: Data on 13,940 Hospitalized Patients from the Spanish Nationwide SEMI-COVID-19 Registry

(1) Objectives: To describe the clinical characteristics and clinical course of hospitalized patients with COVID-19 and autoimmune diseases (ADs) compared to the general population. (2) Methods: We used information available in the nationwide Spanish SEMI-COVID-19 Registry, which retrospectively compiles data from the first admission of adult patients with COVID-19. We selected all patients with ADs included in the registry and compared them to the remaining patients. The primary outcome was all-cause mortality during admission, readmission, and subsequent admissions, and secondary outcomes were a composite outcome including the need for intensive care unit (ICU) admission, invasive and non-invasive mechanical ventilation (MV), or death, as well as in-hospital complications. (3) Results: A total of 13,940 patients diagnosed with COVID-19 were included, of which 362 (2.6%) had an AD. Patients with ADs were older, more likely to be female, and had greater comorbidity. On the multivariate logistic regression analysis, which involved the inverse propensity score weighting method, AD as a whole was not associated with an increased risk of any of the outcome variables. Habitual treatment with corticosteroids (CSs), age, Barthel Index score, and comorbidity were associated with poor outcomes. Biological disease-modifying anti-rheumatic drugs (bDMARDs) were associated with a decrease in mortality in patients with AD. (4) Conclusions: The analysis of the SEMI-COVID-19 Registry shows that ADs do not lead to a different prognosis, measured by mortality, complications, or the composite outcome. Considered individually, it seems that some diseases entail a different prognosis than that of the general population. Immunosuppressive/immunoregulatory treatments (IST) prior to admission had variable effects

Preservation of anti-SARS-CoV-2 neutralising antibodies in convalescent plasma after pathogen reduction with methylene blue and visible light

Background - COVID-19 convalescent plasma (CCP) is an experimental treatment against SARS-CoV-2. Although there has so far been no evidence of transmission through transfusion, pathogen reduction technologies (PRT) have been applied to CCP to mitigate risk of infectious disease. This study aims to assess the impact of methylene blue (MB) plus visible light PRT on the virus-neutralising activity of the specific antibodies against SARS-CoV-2. Material and methods - Thirty-five plasma doses collected by plasmapheresis from COVID-19 convalescent donors were subjected to MB plus visible light PRT. Anti-SARS-CoV-2 RBD S1 epitope IgGs antibodies were quantified by ELISA. Titres of SARS-CoV-2 neutralising antibodies (NtAbs) were measured before and after the PRT process. A Spearman's correlation was run to determine the relationship between antibody neutralisation ability and SARS-CoV-2 IgG ELISA ratio. Pre- and post-inactivation neutralising antibody titres were evaluated using a Wilcoxon test. Results - The plasma pathogen reduction procedure did not diminish NtAbS titres and so did not cause a change in the viral neutralisation capacity of CCP. There was a strong correlation between pre-and post-PRT NtAbs and anti-SARS-CoV-2 IgGs titres. Discussion - Our results showed PRT with MB did not impair the CCP passive immunity preserving its potential therapeutic potency. Therefore, PRT of CCP should be recommended to mitigate the risk for transmission of transfusionassociated infectious disease. There is a good correlation between SARS-CoV-2 IgG titres determined by ELISA and the neutralising capacity. This allows blood centres to select CCP donors based on IgG ELISA titres avoiding the much more labour-intensive laboratory processes for determining neutralising antibodies.Peer reviewe

Dietary diversity and depression: cross-sectional and longitudinal analyses in Spanish adult population with metabolic syndrome. Findings from PREDIMED-Plus trial

Objective: To examine the cross-sectional and longitudinal (2-year follow-up) associations between dietary diversity (DD) and depressive symptoms. Design: 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. Setting: Spanish older adults with metabolic syndrome (MetS). Participants: A total of 6625 adults aged 55–75 years from the PREDIMED-Plus study with overweight or obesity and MetS. Results: 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)). Conclusions: 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.T The PREDIMED-Plus trial was supported by the European Research Council (Advanced Research Grant 2013-2018; 340918) grant to Miguel Angel Martinez-Gonzalez, and by the official funding agency for biomedical research of the Spanish Government, ISCIII through the Fondo de Investigacion para la Salud (FIS), which is cofunded by the European Regional Development Fund (four coordinated FIS projects led by Jordi Salas-Salvado and Josep Vidal), including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, The Especial Action Project entitled: 'Implementacion y Evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus' grant to Jordi Salas-Salvado, the Recercaixa grant to Jordi Salas-Salvado (2013ACUP00194), grants from the Consejeria de Salud de la Junta de Andalucia (PI0458/2013; PS0358/2016; PI0137/2018), the PROMETEO/2017/017 grant from the Generalitat Valenciana, the SEMERGEN grant, and CIBEROBN and FEDER funds (CB06/03), ISCIII. International Nut&Dried Fruit Council-FESNAD N degrees 201302: Miguel Angel Martinez-Gonzalez (PI). None of the funding sources took part in the design, collection, analysis or interpretation of the data, or in the decision to submit the manuscript for publication. The corresponding author had full access to all the data in the study and had final responsibility to submit for publication

Psychometric characteristics of the Spanish version of instruments to measure neck pain disability

[EN] Background. The NDI, COM and NPQ are evaluation instruments for disability due to NP. There was no Spanish version of NDI or COM for which psychometric characteristics were known. The objectives of this study were to translate and culturally adapt the Spanish version of the Neck Disability Index Questionnaire (NDI), and the Core Outcome Measure (COM), to validate its use in Spanish speaking patients with non-specific neck pain (NP), and to compare their psychometric characteristics with those of the Spanish version of the Northwick Pain Questionnaire (NPQ). Methods. Translation/re-translation of the English versions of the NDI and the COM was done blindly and independently by a multidisciplinary team. The study was done in 9 primary care Centers and 12 specialty services from 9 regions in Spain, with 221 acute, subacute and chronic patients who visited their physician for NP: 54 in the pilot phase and 167 in the validation phase. Neck pain (VAS), referred pain (VAS), disability (NDI, COM and NPQ), catastrophizing (CSQ) and quality of life (SF-12) were measured on their first visit and 14 days later. Patients' self-assessment was used as the external criterion for pain and disability. In the pilot phase, patients' understanding of each item in the NDI and COM was assessed, and on day 1 test-retest reliability was estimated by giving a second NDI and COM in which the name of the questionnaires and the order of the items had been changed. Results. Comprehensibility of NDI and COM were good. Minutes needed to fill out the questionnaires [median, (P25, P75)]: NDI. 4 (2.2, 10.0), COM: 2.1 (1.0, 4.9). Reliability: [ICC, (95%CI)]: NDI: 0.88 (0.80, 0.93). COM: 0.85 (0.75,0.91). Sensitivity to change: Effect size for patients having worsened, not changed and improved between days 1 and 15, according to the external criterion for disability: NDI: -0.24, 0.15, 0.66; NPQ: -0.14, 0.06, 0.67; COM: 0.05, 0.19, 0.92. Validity: Results of NDI, NPQ and COM were consistent with the external criterion for disability, whereas only those from NDI were consistent with the one for pain. Correlations with VAS, CSQ and SF-12 were similar for NDI and NPQ (absolute values between 0.36 and 0.50 on day 1, between 0.38 and 0.70 on day 15), and slightly lower for COM (between 0.36 and 0.48 on day 1, and between 0.33 and 0.61 on day 15). Correlation between NDI and NPQ: r = 0.84 on day 1, r = 0.91 on day 15. Correlation between COM and NPQ: r = 0.63 on day 1, r = 0.71 on day 15. Conclusion. Although most psychometric characteristics of NDI, NPQ and COM are similar, those from the latter one are worse and its use may lead to patients' evolution seeming more positive than it actually is. NDI seems to be the best instrument for measuring NP-related disability, since its results are the most consistent with patient's assessment of their own clinical status and evolution. It takes two more minutes to answer the NDI than to answer the COM, but it can be reliably filled out by the patient without assistanceS

Plan de formación docente de jóvenes investigadores pre- y postdoctorales del Departamento de Farmacología y Toxicología.

Los objetivos que se han alcanzado son los siguientes: 1. Teniendo en cuenta los resultados obtenidos durante el curso 2018-19 (además de los resultados obtenidos en el curso 2017-18) los participantes han alcanzado una formación por encima de lo esperado en Farmacología habiendo asistido a una media de 57% del curso en su primer año de participación (cuando lo estipulado en el Plan de Formacion Docente es del 30%). Además, han superado un 42,3% de la materia entre su primer y segundo año con una calificación media de 8,3. 2. Los jóvenes investigadores han realizado una media de 10 horas de prácticas docentes contabilizando aquellas dedicadas a la asistencia a prácticas como oyentes, el ensayo de las prácticas con tutores y la impartición misma de las sesiones de prácticas. El número de horas está muy limitado por el bajo número de horas prácticas en las asignaturas de Farmacología del Dpto. y el elevado número de jóvenes investigadores incorporados al Dpto. 3. Con todo lo anterior, los jóvenes investigadores han alcanzado la formación en competencias docentes y las horas realizadas han sido acreditadas a las respectivas autoridades de sus becas/contratos. Su participación en la docencia práctica les permitirá en el futuro solicitar un certificado de actividades docentes emitido por las autoridades académicas de la Facultad de Medicina que avalaran su experiencia docente en solicitudes de acreditación a las diferentes figuras de profesor ante la ANECA. Además, el Dpto. de Farmacología y Toxicología ha emitido informes detallados de Aptitud Docente en Farmacología reflejando su participación en el Plan de Formación Docente del Dpto. que podrán ser consideradas en solicitudes a puestos docentes en el futuro