Metal-free intermolecular azide-alkyne cycloaddition promoted by glycerol

Metal-free intermolecular Huisgen cycloadditions using nonactivated internal alkynes have been successfully performed in neat glycerol, both under thermal and microwave dielectric heating. In sharp contrast, no reaction occurs in other protic solvents, such as water, ethanol, or diols. DFT calculations have shown that the BnN3/glycerol adduct promotes a more important stabilization of the corresponding LUMO than that produced in the analogous BnN3/alcohol adducts, favoring the reactivity with the alkyne in the first case. The presence of copper salts in the medium did not change the reaction pathway (Cu(I) acts as spectator), except for disubstituted silylalkynes, for which desilylation takes place in contrast to the metal-free system

Key non-metal ingredients for Cu-catalyzed 'Click' reactions in glycerol: nanoparticles as efficient forwarders

The effect of long‐alkyl‐chain amines in CuI‐assisted azide-alkyne cycloadditions of terminal alkynes with organic azides in glycerol and other environmentally benign solvents (water, ethanol) has been examined. The presence of these additives favors the in situ formation of CuI‐based nanoparticles and results in an increase of the catalytic reactivity. In glycerol, liquid‐phase transmission electron microscopy (TEM) analyses, enabled by the negligible vapor pressure of this solvent, proved that CuI nanoparticles are responsible for the observed catalytic activity. The wide variety of alkynes and azides of which this effect has been investigated (14 combinations) confirms the role played by these additives in Cu‐catalyzed Huisgen cycloadditions

SDG localisation and decentralised development aid: exploring opposing discourses and practices in Valencia's aid sector

The approval of the 2030 Agenda and the Sustainable Development Goals (SDGs) has generated intense debates in the aid sector at the global, national and subnational levels. A key question is whether they can address structural problems in development aid policies and practices, such as the lack of accountability and coherence, unequal power relations, or depoliticisation. It seems that this will depend on how the agenda is adopted in the various territories as well as on the different interests at play. We address this question by studying the case of the Valencian Autonomous region. This is the territory in Spain where institutions have been the most active in establishing the SDGs at the core of the political discourses. We follow a qualitative methodology based on semi-structured interviews with key respondents from the public, civil society and university sectors, participant observation, and the analysis of secondary information. Inspired by critical discourse analysis, we explore the varying and conflicting discourses regarding the potential of SDGs to address the problems of aid, and on the impacts that its adoption are producing. We illustrate that the introduction of SDGs in aid policies is a conflictive process modelled by the power dynamics

Stereoselective aminoxylation of biradical titanium enolates with TEMPO

A highly efficient and straightforward aminoxylation of titanium(IV) enolates from (S)-N-acyl-4-benzyl-5,5-dimethyl-1,3-oxazolidin-2-ones with TEMPO has been developed. A wide array of functional groups on the acyl moiety, including alkyl and aryl substituents, olefins, esters, or a-cyclopropyl, as well as a-trifluoromethyl groups, are well tolerated. This transformation can therefore produce the a-aminoxylated adducts in excellent yields with high diastereomeric ratios (d.r.). In turn, parallel additions to the a,b-unsaturated N-acyl counterparts give the corresponding g-adducts with complete regioselectivity in moderate to good yields. Removal of the piperidinyl moiety or the chiral auxiliary converts the resultant adducts into enantiomerically pure a-hydroxy carboxyl derivatives, alcohols, or esters in high yields under mild conditions. Finally, a new mechanistic model based on the biradical character of the titanium(IV) enolates has been proposed

Assessment of inflammation in patients with rheumatoid arthritis using thermography and machine learning: a fast and automated technique

Objectives Sensitive detection of joint inflammation in rheumatoid arthritis (RA) is crucial to the success of the treat-to-target strategy. In this study, we characterise a novel machine learning-based computational method to automatically assess joint inflammation in RA using thermography of the hands, a fast and non-invasive imaging technique. Methods We recruited 595 patients with arthritis and osteoarthritis, as well as healthy subjects at two hospitals over 4 years. Machine learning was used to assess joint inflammation from the thermal images of the hands using ultrasound as the reference standard, obtaining a Thermographic Joint Inflammation Score (ThermoJIS). The machine learning model was trained and tuned using data from 449 participants with different types of arthritis, osteoarthritis or without rheumatic disease (development set). The performance of the method was evaluated based on 146 patients with RA (validation set) using Spearman's rank correlation coefficient, area under the receiver-operating curve (AUROC), average precision, sensitivity, specificity, positive and negative predictive value and F1-score. Results ThermoJIS correlated moderately with ultrasound scores (grey-scale synovial hypertrophy=0.49, p<0.001; and power Doppler=0.51, p<0.001). The AUROC for ThermoJIS for detecting active synovitis was 0.78 (95% CI, 0.71 to 0.86; p<0.001). In patients with RA in clinical remission, ThermoJIS values were significantly higher when active synovitis was detected by ultrasound. Conclusions ThermoJIS was able to detect joint inflammation in patients with RA, even in those in clinical remission. These results open an opportunity to develop new tools for routine detection of joint inflammation

Les ocupacions prehistòriques a les Coves de l'Aumediella (Benifallet) : una visió sintètica

Les coves de l'Aumediella, situades en un dels meandres del riu Ebre a l'alçada de Benifallet (Baix Ebre), han estat fruit de diverses troballes d'interès arqueològic, ben documentades des d'inicis del segle XX. El treballs centrats en el reestudi dels materials arqueològics recuperats, principalment ceràmica, lític i macrolític, ha aportat noves dades relacionades amb les activitats de freqüentació i ús d'aquest conjunt de 6 cavitats. En aquest sentit, el present article es centra en sintetitzar i contextualitzar les principals aportacions dels materials arqueològics recuperats amb l'objectiu contribuir al coneixement de les comunitats del VI-II mil·lenni al tram baix del riu Ebre.The Aumediella's caves, located in a meander of the Ebro River in its passage by Benifallet (Baix Ebre), have generated several findings of archaeological interest, well documented from the early twentieth century. This work is centered on the revision and restudying of this recovered archaeological remains, being them mainly pottery, lithic implements and grinding stones, and has provided new data related to the activities of frequentation and use of this set of six cavities. In this sense, this article is focused on synthetizing and contextualizing the main contributions of this archaeological remains in order to contribute to the knowledge of the 6th to 2n Millennium communities in the lower stretch of the Ebro River

Estudi sobre indicadors de mort a escorxadors catalans

Escorxadors; Benestar animal; Mort; Control oficialMataderos; Bienestar animal; Muerte; Control oficialSlaughterhouses; Animal welfare; Death; Official controlL’anterior treball de la Comunitat de Pràctica (CoP) de Benestar Animal va avaluar el compliment del Reglament (CE) 1099/2009, relatiu a la protecció dels animals en el moment de la matança, mitjançant una enquesta adreçada als serveis veterinaris oficials d’escorxador (SVOE) i que va ser contestada pels companys de 43 escorxadors arreu del territori català que incloïen 64 línies de sacrifici. Es va observar entre les respostes dels SVOE que en 16 de les 64 línies d’algunes de les espècies sacrificades, independentment que s’hi fes un bon atordiment, hi havia un nombre significatiu d’animals que podien presentar signes de vida a l’inici de la preparació de la canal. En part, aquesta deficiència es pot atribuir a la idea estesa que en la fase de sacrifici és suficient aplicar un bon atordiment per aconseguir que no hi hagi signes de vida. No obstant això, l’apartat 3 de l’annex III del Reglament esmentat indica clarament que “la preparació de la canal o l’escaldada només s’han d’efectuar quan s’hagi comprovat la falta de signes de vida de l’animal”. Per tant, no sols cal vetllar per un correcte atordiment en la fase de matança, sinó que també cal comprovar la mort de l’animal abans d’iniciar la preparació de la canal mitjançant l’absència de signes de vida. El treball d’aquesta CoP estudia aquesta fase de mort de l’animal prèvia a la preparació de la canal o l’escaldada, que representa un punt crític de benestar animal a l’escorxador.El anterior trabajo de la Comunidad de Práctica (CoP) de Bienestar Animal evaluó el cumplimiento del Reglamento (CE) 1099/2009, relativo a la protección de los animales en el momento de la matanza, mediante una encuesta dirigida a los servicios veterinarios oficiales de matadero (SVOE) y que fue contestada por los compañeros de 43 mataderos en todo el territorio catalán que incluían 64 líneas de sacrificio. Se observó entre las respuestas de los SVOE que en 16 de las 64 líneas de algunas de las especies sacrificadas, independientemente de que se hiciera un buen aturdimiento, había un número significativo de animales que podían presentar signos de vida al inicio de la preparación de la canal. En parte, esta deficiencia puede atribuirse a la idea extendida de que en la fase de sacrificio es suficiente aplicar un buen aturdimiento para conseguir que no haya signos de vida. No obstante, el apartado 3 del anexo III del citado Reglamento indica claramente que “la preparación de la canal o escaldada sólo deben efectuarse cuando se haya comprobado la falta de signos de vida del animal”. Por tanto, no sólo hay que velar por un correcto aturdimiento en la fase de matanza, sino que también es necesario comprobar la muerte del animal antes de iniciar la preparación de la canal mediante la ausencia de signos de vida. El trabajo de esta CoP estudia esta fase de muerte del animal previa a la preparación de la canal o escaldada, que representa un punto crítico de bienestar animal en el matadero.The previous work of the Animal Welfare Community of Practice (CoP) evaluated compliance with Regulation (EC) 1099/2009, regarding the protection of animals at the time of slaughter, through a survey addressed to the official veterinary services of slaughterhouse (SVOE) and that was answered by colleagues from 43 slaughterhouses throughout the Catalan territory that included 64 slaughter lines. It was observed among the responses of the SVOE that in 16 of the 64 lines of some of the species sacrificed, regardless of whether a good stunning was done, there was a significant number of animals that could show signs of life at the beginning of the preparation of the stunning. channel. In part, this deficiency can be attributed to the widespread idea that in the slaughter phase it is enough to apply a good stun to ensure that there are no signs of life. However, section 3 of annex III of the aforementioned Regulation clearly indicates that "the preparation of the carcass or scalding must only be carried out when the lack of signs of life of the animal has been verified". Therefore, it is not only necessary to ensure correct stunning in the slaughter phase, but it is also necessary to verify the death of the animal before starting the preparation of the carcass through the absence of signs of life. The work of this CoP studies this phase of death of the animal prior to the preparation of the carcass or scalding, which represents a critical point of animal welfare in the slaughterhouse

Comparison of Migration Disturbance Potency of Epigallocatechin Gallate (EGCG) Synthetic Analogs and EGCG PEGylated PLGA Nanoparticles in Rat Neurospheres

Epigallocatechin gallate (EGCG), the main catechin of green tea, is described to have potential health benefits in several fields like oncology, neurology or cardiology. Currently, it is also under pre-clinical investigation as a potential therapeutic or preventive treatment during pregnancy against developmental adverse effects induced by toxic substances. However, the safety of EGCG during pregnancy is unclear due to its proven adverse effects on neural progenitor cells' (NPCs) migration. As lately several strategies have arisen to generate new therapeutic agents derived from EGCG, we have used the rat 'Neurosphere Assay' to characterize and compare the effects of EGCG structurally related compounds and EGCG PEGylated PLGA nanoparticles on a neurodevelopmental key event: NPCs migration. Compounds structurally-related to EGCG induce the same pattern of NPCs migration alterations (decreased migration distance, decreased formation of migration corona, chaotic orientation of cellular processes and decreased migration of neurons at higher concentrations). The potency of the compounds does not depend on the number of galloyl groups, and small structure variations can imply large potency differences. Due to their lower toxicity observed in vitro in NPCs, 4,4′-bis[(3,4,5-trihydroxybenzoyl)oxy]-1,1′-biphenyl and EGCG PEGylated PLGA nanoparticles are suggested as potential future therapeutic or preventive alternatives to EGCG during prenatal period

Mediterranean Diet and Atherothrombosis Biomarkers: A Randomized Controlled Trial

Scope To assess whether following a Mediterranean diet (MedDiet) improves atherothrombosis biomarkers in high cardiovascular risk individuals. Methods and results In 358 random volunteers from the PREvención con DIeta MEDiterránea trial, the 1‐year effects on atherothrombosis markers of an intervention with MedDiet, enriched with virgin olive oil (MedDiet‐VOO; n = 120) or nuts (MedDiet‐Nuts; n = 119) versus a low‐fat control diet (n = 119), and whether large increments in MedDiet adherence (≥3 score points, versus compliance decreases) and intake changes in key food items are associated with 1‐year differences in biomarkers. Differences are observed between 1‐year changes in the MedDiet‐VOO intervention and control diet on the activity of platelet activating factor acetylhydrolase in high‐density lipoproteins (HDLs) (+7.5% [95% confidence interval: 0.17; 14.8]) and HDL‐bound α1‐antitrypsin levels (−6.1% [−11.8; −0.29]), and between the MedDiet‐Nuts intervention and the control arm on non‐esterified fatty acid concentrations (−9.3% [−18.1; −0.53]). Large MedDiet adherence increments are associated with less fibrinogen (−9.5% [−18.3; −0.60]) and non‐esterified fatty acid concentrations (−16.7% [−31.7; −1.74]). Increases in nut, fruit, vegetable, and fatty fish consumption, and decreases in processed meat intake are linked to enhancements in biomarkers. Conclusion MedDiet improves atherothrombosis biomarkers in high cardiovascular risk individuals.This work was supported by grants of Instituto de Salud Carlos III [OBN17PI02, PIE14/00045_INFLAMES, CB06/03/0019, CB06/03/0028, and CD17/00122 (A.H.)], and Agència de Gestió d'Ajuts Universitaris i de Recerca (2017 SGR 222)