Acoplamientos catalizados por paladio en cationes heteroaromáticos: síntesis y propiedades ópticas no lineales de cromóforos catiónicos

Texto en español y resumen en inglésThe development of new organic materials with nonlinear optical properties (NLO) was one of the aims of research over the past decades due to their potential use in the field of telecommunications, optical computing and processing and optical data storage, among others. The advantages of organic compounds compared to inorganic crystals are its low cost, ease of processing and high number of structural variability, which makes them very attractive to industry. Most organic compounds with non-linear optical (NLO) properties are based on highly conjugated molecules with donors and acceptors substituted at the two ends of the molecule, called donor-acceptor (?push-pull?) systems, and these are amongst the most interesting structures for new compounds with efficient NLO responses. The PhD project presented in this report is framed in the context of a search for new molecules push-pull type, based on heteroaromatic cations as acceptors of the system (for these systems has been appointed a new name as "NLO-catiophores), and partly in the development of the synthesis of new macrocyclic rigid cationic nature. First we describe the synthesis and study of nonlinear optical properties by Hyper-Rayleigh Scattering (HRS) of new push-pull system based on heteroaromatic cations. They were obtained through the development of the Suzuki, Heck and Sonogashira reactions. We have demonstrated that organotrifluroborates are better efficient partners than boronic acids for the Suzuki coupling reaction with pyridinium and, Moreover, the ease with which these potassium organotrifluoroborates reacted with azinium and quinolizinium salts in water and the coupling products can be isolated is a further advantage of the procedure and provides a new means for accessing to a great variety of substituted cations. It has proved possible to Heck coupling with aryl iodides with the four isomers of vinilquinolizinium. We have achived the synthesis of a series of D-A and D-A-D catio-phores by Sonogashira cross-coupling reaction from aziniun and quinolizinium bromoderivatives. Noting the overall study ONL values of selected molecules can be obtained the following conclusions: a) heteroaromatic cations type azinium and quinolizinium have good NLO properties (βHRS values between 25-500 10-30 esu). In general, for the pyridinium cation, substitution at the C4 produces best response NLO and in case of cation quinolizinium position C2 is best. b) electrodonating substituent favor the charge transfer on the system Donnor-Acceptor. Moreover it was found that the quinolizinium cation is better acceptor increasing the value of hyperpolarizability. On the other hand, in this context of development of new materials, we considered introducing the quinolizinium system on macrocyclic structures shape-persistent type, i.e. a rigid skeleton formed by aryl units linked together by triple bonds, which resulting in large molecular surfaces. These properties make the AEMs (arylene-ethynylene macrocycles), structures of interest in the field of organic materials

Acoplamientos catalizados por paladio en cationes heteroaromáticos: síntesis y propiedades ópticas no lineales de cromóforos catiónicos

Texto en español y resumen en inglésThe development of new organic materials with nonlinear optical properties (NLO) was one of the aims of research over the past decades due to their potential use in the field of telecommunications, optical computing and processing and optical data storage, among others. The advantages of organic compounds compared to inorganic crystals are its low cost, ease of processing and high number of structural variability, which makes them very attractive to industry. Most organic compounds with non-linear optical (NLO) properties are based on highly conjugated molecules with donors and acceptors substituted at the two ends of the molecule, called donor-acceptor (?push-pull?) systems, and these are amongst the most interesting structures for new compounds with efficient NLO responses. The PhD project presented in this report is framed in the context of a search for new molecules push-pull type, based on heteroaromatic cations as acceptors of the system (for these systems has been appointed a new name as "NLO-catiophores), and partly in the development of the synthesis of new macrocyclic rigid cationic nature. First we describe the synthesis and study of nonlinear optical properties by Hyper-Rayleigh Scattering (HRS) of new push-pull system based on heteroaromatic cations. They were obtained through the development of the Suzuki, Heck and Sonogashira reactions. We have demonstrated that organotrifluroborates are better efficient partners than boronic acids for the Suzuki coupling reaction with pyridinium and, Moreover, the ease with which these potassium organotrifluoroborates reacted with azinium and quinolizinium salts in water and the coupling products can be isolated is a further advantage of the procedure and provides a new means for accessing to a great variety of substituted cations. It has proved possible to Heck coupling with aryl iodides with the four isomers of vinilquinolizinium. We have achived the synthesis of a series of D-A and D-A-D catio-phores by Sonogashira cross-coupling reaction from aziniun and quinolizinium bromoderivatives. Noting the overall study ONL values of selected molecules can be obtained the following conclusions: a) heteroaromatic cations type azinium and quinolizinium have good NLO properties (βHRS values between 25-500 10-30 esu). In general, for the pyridinium cation, substitution at the C4 produces best response NLO and in case of cation quinolizinium position C2 is best. b) electrodonating substituent favor the charge transfer on the system Donnor-Acceptor. Moreover it was found that the quinolizinium cation is better acceptor increasing the value of hyperpolarizability. On the other hand, in this context of development of new materials, we considered introducing the quinolizinium system on macrocyclic structures shape-persistent type, i.e. a rigid skeleton formed by aryl units linked together by triple bonds, which resulting in large molecular surfaces. These properties make the AEMs (arylene-ethynylene macrocycles), structures of interest in the field of organic materials

Efficient functionalization of quinolizinium cations with organotrifluoroborates in water

An efficient functionalization of the quinolizinium system is reported. The reaction of the four isomeric bromoquinolizinium salts with different organotrifluoroborates afforded alkyl-, vinyl-, aryl-, and heteroaryl quinolizinium derivatives in moderate or good yields. Reactions are carried out in water using a counterion exchange for the isolation of the cationic-coupled compounds.Comunidad de Madri

A Comprehensive Framework to Reinforce Evidence Synthesis Features in Cloud-Based Systematic Review Tools

Systematic reviews are powerful methods used to determine the state-of-the-art in a given field from existing studies and literature. They are critical but time-consuming in research and decision making for various disciplines. When conducting a review, a large volume of data is usually generated from relevant studies. Computer-based tools are often used to manage such data and to support the systematic review process. This paper describes a comprehensive analysis to gather the required features of a systematic review tool, in order to support the complete evidence synthesis process. We propose a framework, elaborated by consulting experts in different knowledge areas, to evaluate significant features and thus reinforce existing tool capabilities. The framework will be used to enhance the currently available functionality of CloudSERA, a cloud-based systematic review tool focused on Computer Science, to implement evidence-based systematic review processes in other disciplines.This research was funded by the Spanish Research Agency (Agencia Estatal de Investigacion) with ERDF funds grant number TIN2017-85797-R (VISAIGLE project). The research stay of T. Person in the SFU was funded by Erasmus+ KA107 grant number 2017-1-ES01-KA107-037422. The APC was funded by the VISAIGLE project

The effect of smoking on clinical parameters and structural damage in patients with axial spondyloarthritis: a systematic literature review.

Objectives: To evaluate the association between smoking and clinical parameters and structural damage in axial spondyloarthritis (axSpA). Methods: We systematically searched MEDLINE, EMBASE and Cochrane Library up to November 2015. We selected articles that analysed the smoking impact on disease activity, functional status, structural damage, physical mobility and life quality. Independent extraction of articles by 2 authors using predefined data fields was performed. Studies quality was graded according to the Oxford Level of Evidence scale. Results: A total of 17 articles were selected for inclusion: 2 case-control, 11 cross sectional and 4 prospective cohort studies, which analysed 4,694 patients. Weak evidence suggested a smoking effect on pain, overall assessment of health, disease activity, physical mobility and life quality in ankylosing spondylitis (AS). Moderate-good evidence revealed higher HAQ-AS among smokers (0.025 units/yr, 95%CI: 0.0071-0.0429, p=0.007). Every additional unit of ASDAS resulted in an increase of 1.9 vs. 0.4 mSASSS units/2 yr in AS smokers vs. non-smokers. Good evidence revealed that cigarette smoking and smoking intensity was associated with spinal radiographic progression in axSpA [mSASSS ≥2 units/2 yr: OR=2.75, 95%CI: 1.25-6.05, p=0.012; mSASSS progression in heavy smokers (> 10 cigarettes/day): OR=3.57, 95%IC: 1.33-9.60, p=0.012]. Conclusions: Published data indicate that smoking has a dose-dependent impact on structural damage progression in axSpA. There is worse HAQ among AS smokers compared to non-smokers. Respect to pain, overall assessment of health, disease activity, physical mobility and life quality, although the evidence level is poor, all evidence points in the same direction: smoking AS patients are worse than non-smoking.pre-print260 K

The Influence of the COVID-19 Pandemic on the Clinical Application of Evidence-Based Practice in Health Science Professionals

(1) Background: Evidence-based practice (EBP) informs daily clinical interventions with the purpose of seeking changes to traditional practice through scientific evidence that justifies the reasons for our actions. The objectives were to describe the barriers, beliefs, and attitudes in the application of EBP among university health professionals (not doctors) and to evaluate the influence of the COVID-19 pandemic among them. (2) Methods: This prospective study is both descriptive and observational. The individuals under study were university health professionals (not doctors) from various autonomous regions within Spain, in both public and private spheres. Sociodemographic and labor-related variables linked to the research and its completion were studied. Likewise, the survey instrument Health Sciences Evidence-Based Practice questionnaire (HS-EBP) was administered to evaluate the barriers to, beliefs in, and attitudes towards evidence-based practice. (3) Results: A total of 716 responses were gathered, of which 387 were collected during the period of confinement, and 343 in the COVID-19 post-confinement period. Possible associations that might help respond to the objectives were explored through a correlational study between the sociodemographic variables and each sub-scale of the HS-EBP 30 questionnaire (n = 716). (4) Conclusions: Barriers to, beliefs in, and attitudes towards evidence-based practice are described. There is a leadership gap where line management provides insufficient motivation to follow work routines. The COVID-19 pandemic has caused immense stress among health professionals. The post-confinement group showed a significant change in the variables "beliefs and attitudes", and likewise in the "evaluation" block, justified by the need to update knowledge and to apply evidence.This project has been financed with the help of IDIVAL, Project number NVAL 19/04 through the Marqués de Valdecilla Research Institute, IDIVAL, Spain

Influence of HLA DRB1 alleles in the susceptibility of rheumatoid arthritis and the regulation of antibodies against citrullinated proteins and rheumatoid factor

25 pages, 2 figures, 5 tables.-- Provisional PDF.[Introduction] To investigate the association between HLA-DRB1 alleles with susceptibility to rheumatoid arthritis (RA) and production of antibodies against citrullinated proteins (ACPA) and rheumatoid factor (RF).[Methods] We studied 408 patients (235 with RA, 173 non-RA) and 269 controls. ACPA, RF and HLA-DR typing were determined.[Results] We found an increased frequency of HLA DRB1 alleles with the shared epitope (SE) in ACPA-positive RA. Inversely, HLA DRB1 alleles encoding DERAA sequences were more frequent in controls than in ACPA-positive RA, and a similar trend was found for HLA DR3. However these results could not be confirmed after stratification for the presence of the SE, probably due to the relatively low number of patients. These data may suggest that the presence of these alleles may confer a protective role for ACPA-positive RA. In RA patients we observed association between SE alleles and ACPA titers in a dose-dependent effect. The presence of HLA DR3 or DERAA-encoding alleles was associated with markedly reduced ACPA levels. No association between RF titers and HLA DR3 or DERAA-encoding alleles was found.[Conclusions] HLA DRB1 alleles with the SE are associated with production of ACPA. DERAA-encoding HLA-DR alleles and HLA DR3 may be protective for ACPA-positive RA.Supported by Fundacion Mutua Madrileña PI-668 and Beca FER-Abbott 2004.Peer reviewe

Hormonal dependence and cancer in Systemic Lupus Erythematosus

Objective: To estimate the incidence and analyze any cancer-associated factors in patients with systemic lupus erythematosus (SLE), differentiating between hormone-sensitive (HS) and non-HS cancers. Methods: This was a retrospective multicenter study of a patient cohort from the Systemic Lupus Erythematosus Registry of the Spanish Society of Rheumatology. Included were the first cancer post-SLE diagnosis, clinical and sociodemographic information, cumulative damage, severity, comorbidities, treatments, and refractoriness. Cancers were classified as HS (prostate, breast, endometrium, and ovarian) and non-HS (the remainder). The standardized incidence ratio (SIR) was calculated and logistic regression models were built. Results: A total of 3,539 patients (90.4% women) were included, 154 of whom had cancer (91% female), and 44 had HS cancer (100% female). The cancer SIR was 1.37 (95% confidence interval [95% CI] 1.15-1.59), with higher values in women age <65 years (SIR 2.38 [95% CI 1.84-2.91]). The SIR in women with HS versus non-HS cancer was 1.02 (95% CI 0.13-1.91) and 1.93 (95% CI 0.98-2.89). In HS versus non-HS cancers, SLE diagnostic age (odds ratio [OR] 1.04 [P = 0.002] versus 1.04 [P = 0.019]), and period of disease evolution (OR 1.01 [P < 0.001] versus 1.00 [P = 0.029]) were associated with cancer. The Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (OR 1.27 [P = 0.022]) and angiotensin-converting enzyme (ACE) inhibitor prescriptions (OR 2.87 [P = 0.048]) were associated with non-HS cancers. Conclusion: Cancer incidence in patients with SLE was higher than in the Spanish population, particularly among young women. This increase might be due to non-HS cancers, which would be associated with SLE involving greater cumulative damage where more ACE inhibitors are prescribed.The RELESSER Registry was partially funded by GSK, Roche, UCB, Lilly and Novartis. The sponsors had no role in the study design, data collection, analysis or interpretation, in writing the report, or in the decision to submit the article for publication. Dr. Pego-Reigosa is supported by grant 316265 (BIOCAPS) from the European Union 7th Framework Program (FP7/REGPOT-2012- 2013.1). The FIS Grant PI11/02857 (Instituto Carlos III, Fondos FEDER) supported this study

Lipoprotein(A) Concentrations In Rheumatoid Arthritis On Biologic Therapy: Results From The Cardiovascular In Rheumatology [Carma] Study Project

Background Plasma concentrations of lipoprotein (a) (Lp(a)), a lipoprotein with atherogenic and thrombogenic properties, have a strong genetic basis, although high concentrations of Lp(a) have also been reported in the context of inflammation, as in rheumatoid arthritis (RA). Few studies evaluate the impact of biologic therapies (BT) on Lp(a) in RA, taking into account that with these new therapies a better control of inflammation is achieved. Objective The aim of the study was to evaluate the plasma concentrations of Lp(a) in Spanish RA patients on BT attending rheumatology outpatient clinics. Methods Baseline analysis of the CARdiovascular in rheuMAtology project, a 10-year prospective study, evaluating the risk of cardiovascular events in RA and other forms of inflammatory arthritis. RA patients were classified according to treatment: no biologic, anti-tumor necrosis factor, anti-interleukin-6 receptor tocilizumab (TCZ), and other biologic (rituximab or abatacept). A model of linear multivariate regression was built in which the dependent variable was Lp(a) concentration and the explanatory variable was BT. The model was adjusted for confounding factors. Results Seven hundred and seventy-five RA patients were analyzed. Plasma concentrations of total cholesterol and triglyceride were significantly higher in TCZ-treated patients. Nevertheless, no significant difference in the atherogenic index between TCZ-treated patients and patients without BT was found. After adjusting for confounding factors, patients with BT had lower concentrations of Lp(a) than those without BT; however, only TCZ-treated patients achieved statistically significant differences (?: ?0.303, 95% confidence interval: ?0.558 to ?0.047; P = .02). Conclusions RA patients treated with TCZ show lower plasma concentrations of Lp(a) compared with patients without BT.This project has been supported by an unrestricted grant from Abbvie, Spain. The design, analysis, interpretation of results, and preparation of the article have been done independently of Abbvie. Dr González-Gay's studies have been supported by grants from “Fondo de Investigaciones Sanitarias” PI06/0024, PS09/00748, and PI12/00060 and RD12/0009/0013 (RIER) from “Instituto de Salud Carlos III” (ISCIII) (Spain)

Increased risk of MAFLD and liver fibrosis in inflammatory bowel disease independent of classic metabolic risk factors

ackground & Aims There is conflicting evidence regarding the prevalence of and risk factors for metabolic-associated fatty liver disease (MAFLD) in patients with inflammatory bowel disease (IBD). We aimed to determine MAFLD prevalence and risk factors in IBD patients. Methods Cross-sectional, case-control study included all consecutive IBD patients treated at 2 different university hospitals. Controls were subjects randomly selected from the general population and matched by age, sex, type 2 diabetes status, and body mass index in a 1:2 ratio. MAFLD was confirmed by controlled attenuation parameter. Liver biopsies were collected when MAFLD with significant liver fibrosis was suspected. In addition, age- and fibrosis stage-paired non-IBD patients with biopsy-proven MAFLD served as a secondary control group. Results Eight hundred thirty-one IBD patients and 1718 controls were included. The prevalence of MAFLD and advanced liver fibrosis (transient elastography ≥9.7 kPa) was 42.00% and 9.50%, respectively, in IBD patients and 32.77% and 2.31%, respectively, in the general population (P < .001). A diagnosis of IBD was an independent predictor of MAFLD (adjusted odds ratio, 1.99; P < .001) and an independent risk factor for advanced liver fibrosis (adjusted odds ratio, 5.55; P < .001). Liver biopsies were obtained from 40 IBD patients; MAFLD was confirmed in all cases, and fibrosis of any degree was confirmed in 25 of 40 cases (62.5%). Body mass index and type 2 diabetes prevalence were significantly lower in IBD-MAFLD patients than in severity-paired patients with biopsy-proven MAFLD. Conclusions MAFLD and liver fibrosis are particularly prevalent in IBD patients, regardless of the influence of classic metabolic risk factors.Acknowledgements: The authors report funding support from the Spanish Instituto de Salud Carlos III-FEDER Grant (FIS - PI18/01304) related to this manuscript